Thrombospondin-2 (THBS2) – Function, Processes, and Localization OpenAI o3-deep-research-2025-06-26 102 citations 2025-11-04T00:41:29.660788

Thrombospondin-2 (THBS2) – Function, Processes, and Localization

Gene and Protein Overview: The human THBS2 gene encodes thrombospondin-2 (TSP2), an extracellular glycoprotein belonging to the thrombospondin family. Thrombospondin-2 is a large matricellular protein – a class of non-structural extracellular matrix (ECM) proteins that modulate cell–matrix interactions rather than serving as core structural components (pubmed.ncbi.nlm.nih.gov). TSP2 monomers (~145 kDa each) assemble into a homotrimeric complex (pmc.ncbi.nlm.nih.gov). Each TSP2 subunit has a multi-domain architecture, including an N-terminal heparin-binding domain, a procollagen-like region, three type I thrombospondin repeats, three type II EGF-like repeats, seven type III calcium-binding repeats, and a C-terminal globular domain (pmc.ncbi.nlm.nih.gov). These domains confer the ability to bind various molecules and ions (e.g. heparan sulfate, integrins, matrix components, and Ca²⁺) and underlie TSP2’s diverse interactions (pmc.ncbi.nlm.nih.gov).

Localization and Expression: Thrombospondin-2 is a secreted protein that localizes to the extracellular space and ECM of connective tissues. In adults, THBS2 expression is relatively low under basal conditions, but it is present in dermis, cartilage, bone, and blood vessel walls (pmc.ncbi.nlm.nih.gov). TSP2 expression is developmentally regulated – it is synthesized mainly in connective tissues during embryonic development and is induced in adults during tissue remodeling or injury (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Unlike its homolog thrombospondin-1 (TSP1), which is stored in platelets, TSP2 is not normally abundant in platelets; instead, it is produced by stromal cells (e.g. fibroblasts) and deposited into the ECM (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Upon tissue injury or inflammation, local fibroblasts and other cells upregulate TSP2, enriching the wound ECM with this protein (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This spatiotemporal expression pattern allows TSP2 to carry out its functions in interstitial spaces and basement membranes of tissues undergoing repair, remodeling, or development.

ECM Remodeling and Collagen Organization: A primary role of thrombospondin-2 is to modulate the structure and turnover of the extracellular matrix. TSP2 does not itself form fibrils, but influences how other matrix components assemble and degrade (pubmed.ncbi.nlm.nih.gov). Collagen fibrillogenesis is notably affected by TSP2. Mice lacking TSP2 (Thbs2-null) exhibit abnormal collagen fiber morphology and connective tissue defects (pubmed.ncbi.nlm.nih.gov). For example, TSP2-null skin has disorganized or thickened collagen fibrils and manifests as skin fragility and lax tendons/ligaments (pmc.ncbi.nlm.nih.gov). Mechanistically, TSP2 regulates collagen architecture by controlling matrix metalloproteinase activity in the pericellular environment. Thbs2-knockout fibroblasts show abnormally high levels of matrix metalloproteinase-2 (MMP-2) in their culture media (about twice that of normal cells) despite unchanged MMP-2 mRNA, indicating a post-transcriptional regulatory effect (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This excess MMP-2 leads to excessive collagen proteolysis and poor cell–matrix adhesion, as evidenced by the rescued adhesion after adding MMP inhibitors (pmc.ncbi.nlm.nih.gov). Thrombospondin-2 directly binds MMP-2 and forms a complex (potentially including TIMP-2) that is recognized by the low-density lipoprotein receptor-related protein (LRP) on the cell surface (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Through this interaction, TSP2 facilitates the endocytic clearance of MMP-2, targeting the protease for lysosomal degradation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). By sequestering and removing MMP-2 (and possibly other proteases), TSP2 helps maintain matrix integrity – preventing excessive collagen degradation and allowing proper fibril formation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Consistently, re-introduction of TSP2 into TSP2-null fibroblasts normalizes MMP-2 levels and restores healthy cell–matrix adhesion (pmc.ncbi.nlm.nih.gov). In addition to MMP-2, TSP2 has been reported to downregulate other matrix-degrading enzymes. For instance, in cancer cell models TSP2 reduces MMP-9 and urokinase-type plasminogen activator (uPA) expression, limiting cell invasion and metastasis (pmc.ncbi.nlm.nih.gov). In cartilage tissue, TSP2 helps preserve the extracellular matrix by suppressing MMP-13, the enzyme that degrades type II collagen; as a result, TSP2 protects cartilage from breakdown in osteoarthritic conditions (pmc.ncbi.nlm.nih.gov). These findings underscore TSP2’s role as an ECM guardian – it modulates collagen fibrillogenesis and matrix composition by binding structural proteins and regulating protease activity.

Cell Adhesion and Matricellular Interactions: As a matricellular protein, thrombospondin-2 interacts with cells to influence adhesion, migration, and signaling. TSP2 contains an RGD (Arg-Gly-Asp) sequence in its C-terminal region that enables direct binding to certain integrins on cell surfaces (pmc.ncbi.nlm.nih.gov). In particular, TSP2 can engage integrin αvβ3, a receptor on fibroblasts, endothelial cells and chondrocytes (pmc.ncbi.nlm.nih.gov). Through integrin αvβ3> binding, TSP2 can transmit signals into cells: for example, in synovial fibroblasts TSP2 binding to αvβ3 activates the PI3K/Akt and NF-κB pathways, leading to induction of interleukin-6 (IL-6) expression (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). (Blocking αvβ3 or its downstream kinases abolishes TSP2-induced NF-κB activation and IL-6 production (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).) TSP2 can also bind other integrins (e.g. α4β1 and β1-containing integrins) and heparan sulfate proteoglycans, reflecting its multiple interactive motifs (pmc.ncbi.nlm.nih.gov). These adhesive interactions allow TSP2 to bridge cells with the ECM, influencing cell attachment and spreading. Notably, TSP2’s effects on cell adhesion are context-dependent: while exogenous TSP2 can promote cell spreading and chemotaxis in some assays similar to TSP1 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), the absence of TSP2 in vivo leads to cell-matrix attachment defects due to dysregulated proteolysis (as discussed above). Thus, TSP2 helps tune the adhesive microenvironment by binding to cell-surface receptors and matrix ligands, ensuring proper cell anchorage and communication with the ECM.

Regulation of Angiogenesis: One of the defining functions of thrombospondin-2 is its role as a potent inhibitor of angiogenesis (new blood vessel formation). Like TSP1, thrombospondin-2 is classified as an endogenous angiogenesis inhibitor (pmc.ncbi.nlm.nih.gov). However, some evidence suggests TSP2 may exert even stronger anti-angiogenic and anti-tumor effects than TSP1 in certain contexts (pmc.ncbi.nlm.nih.gov). TSP2-deficient mice show increased vascular density in their tissues, underscoring the protein’s normal role in restraining vessel growth (pubmed.ncbi.nlm.nih.gov). For example, Thbs2-null mice have an abnormally high density of microvessels in the skin and subcutaneous tissue (pubmed.ncbi.nlm.nih.gov), and healing wounds in these mice maintain excessive blood vessel networks in the granulation tissue (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In contrast, overexpression of thrombospondins leads to suppressed angiogenesis and smaller vessel size in wound sites (pmc.ncbi.nlm.nih.gov). The anti-angiogenic activity of TSP2 is at least partly mediated through inducing apoptosis in endothelial cells. TSP2’s type I repeats can bind the CD36 receptor on microvascular endothelial cells (similar to TSP1’s mechanism), triggering a cascade that leads to endothelial cell apoptosis and capillary regression (pmc.ncbi.nlm.nih.gov). In vitro, an N-terminal fragment of TSP2 that includes the proper domains was shown to activate CD36 and initiate endothelial apoptosis, inhibiting tumor vascularization and growth in a breast cancer model (pmc.ncbi.nlm.nih.gov). Thus, TSP2 directly counteracts pro-angiogenic signals, helping to limit neovascularization during wound healing and in tumors. Moreover, by regulating proteases and ECM composition, TSP2 creates an environment less favorable to new vessel sprouting (for instance, high TSP2 levels correlate with reduced MMP-9 and VEGF availability in some tumor microenvironments) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The ability of TSP2 to “turn off” angiogenesis is important in physiological contexts (to terminate angiogenesis after tissue repair) and has drawn interest in pathological contexts where excessive angiogenesis is a factor (e.g. cancer, ocular neovascular disorders).

Signaling Pathways and Receptor Interactions: Beyond integrins and CD36, thrombospondin-2 interacts with various signaling molecules. A striking finding is TSP2’s interaction with the Notch signaling pathway, which is critical for cell fate and vascular development. TSP2 (but notably not TSP1) binds directly to Notch3 (a Notch receptor) and its ligand Jagged1, and it enhances their ability to engage (pubmed.ncbi.nlm.nih.gov). By acting as a scaffold that brings Notch3 and Jagged1 together, TSP2 potentiates Notch3 signal transduction (pubmed.ncbi.nlm.nih.gov). In fact, the presence of TSP2 augments Notch3-dependent gene activation, whereas TSP2-knockout mice show reduced expression of Notch target genes (pubmed.ncbi.nlm.nih.gov). Functionally, this Notch-modulating activity of TSP2 has been linked to reduced cancer cell proliferation in a Notch-dependent manner, suggesting TSP2 can influence differentiation or quiescence signals via Notch in certain contexts (pubmed.ncbi.nlm.nih.gov). Thrombospondin-2 also binds growth factors and cytokines indirectly; for example, TSP2 can sequester TGF-β and other cytokines in the matrix, although this role is more established for TSP1. In injury models, overexpression of TSP2 was found to limit active TGF-β levels and inflammation, implying a possible role in controlling growth factor activation (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Furthermore, as mentioned, TSP2 interacts with the endocytic LRP1 receptor to clear MMPs (pmc.ncbi.nlm.nih.gov), and it can bind heparan sulfate proteoglycans which concentrate chemokines and growth factors in the ECM (pmc.ncbi.nlm.nih.gov). Through these diverse interactions, TSP2 serves as a regulatory node in cell signaling networks at the extracellular interface – influencing pathways like MAPK/JNK (via CD36 activation in endothelial cells) (pmc.ncbi.nlm.nih.gov), PI3K/Akt/NF-κB (via integrins in fibroblasts) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), and Notch (via direct ligand–receptor bridging) (pubmed.ncbi.nlm.nih.gov). These signaling effects are context-dependent but collectively contribute to TSP2’s role in coordinating tissue remodeling and cellular responses to the environment.

Role in Development and Tissue Repair: Thrombospondin-2 is crucial for proper tissue development, repair, and homeostasis due to its ECM and signaling functions. During embryonic development, TSP2 is highly expressed in connective tissues and contributes to the organization of dermis, cartilage, and tendon matrices (pmc.ncbi.nlm.nih.gov). Mice lacking TSP2 display developmental phenotypes such as loose skin and hyperextensible joints (reflecting collagen fibril aberrations) and an enhanced vascularization in tissues like skin and adipose (pmc.ncbi.nlm.nih.gov). In wound healing, TSP2 is dynamically regulated: its expression in fibroblasts rises a few days after injury and peaks during the formation and maturation of granulation tissue (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Functionally, TSP2 acts to restrain the wound healing process to ensure proper tissue repair. Thbs2-null wounds in mice close faster with quicker scab loss, but they exhibit excessive granulation tissue, persistently elevated blood vessel density, and disorganized collagen deposition (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This suggests that in normal wounds, TSP2 helps tone down fibrovascular proliferation and encourages matrix organization as healing progresses. Conversely, when TSP2 is overexpressed (or when the related TSP1 is transgenically increased), wound closure is delayed and angiogenesis is dampened, reinforcing the idea that thrombospondins serve to limit overzealous repair responses for optimal scar formation (pmc.ncbi.nlm.nih.gov). In the context of cartilage and bone, TSP2 has emerged as an important factor as well. It is strongly expressed in developing cartilage and upregulated in osteoarthritic cartilage, implying a role in cartilage maintenance or repair (pmc.ncbi.nlm.nih.gov). Studies show that TSP2 can promote chondrocyte differentiation from mesenchymal stem cells and protect cartilage from inflammatory damage (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). By binding to specific receptors on chondrocytes and modulating signaling (such as TGF-β/Smad and integrin pathways), TSP2 supports cartilage matrix production and stability (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In line with this, TSP2-neutralizing antibodies worsened cartilage degeneration in an osteoarthritis model, while adding exogenous TSP2 improved cartilage repair indices (pmc.ncbi.nlm.nih.gov). These observations identify TSP2 as a critical regulator in tissue remodeling, balancing matrix synthesis and degradation, vascular growth, and cellular differentiation during both development and healing.

Pathophysiological and Clinical Notes: Given its roles, THBS2 has been implicated in various diseases, especially those involving aberrant ECM remodeling or angiogenesis. Cancer: Many tumors alter stromal TSP2 levels; high TSP2 generally correlates with suppressed tumor vascularization and slower tumor progression, whereas loss of TSP2 can facilitate invasive growth (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). For example, clinical studies in lung, pancreatic, and other cancers found that TSP2 is a negative regulator of tumor aggressiveness, often associated with lower MMP-9 levels and reduced cancer cell proliferation (pmc.ncbi.nlm.nih.gov). Experimentally, restoring TSP2 in aggressive cancer models has inhibited angiogenesis and metastasis, highlighting its potential as an anti-angiogenic therapeutic target (pmc.ncbi.nlm.nih.gov). Fibrotic and vascular diseases: Because TSP2 modulates TGF-β activation and matrix deposition, it may influence fibrosis. In a chronic nephropathy model, TSP2 gene therapy reduced TGF-β activation, inflammation, and angiogenesis, ameliorating kidney fibrosis (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Orthopedic and connective tissue disorders: Mutations in THBS2 or dysregulation of its expression have been linked to connective tissue abnormalities. Notably, rare human THBS2 mutations were recently associated with a form of Ehlers–Danlos syndrome involving tendon and ligament laxity, consistent with the phenotypes of Tsp2-null mice (though such mutations are uncommon) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In osteoarthritis, elevated TSP2 in joint tissues appears to be a compensatory response attempting to limit cartilage breakdown (pmc.ncbi.nlm.nih.gov). Finally, mechanobiology studies suggest TSP2 is part of the tissue’s response to mechanical stress – for instance, altered TSP2 signaling (through integrin–cytoskeleton pathways) can affect cell stiffness and cytoskeletal organization under diabetic or high stress conditions (biosignaling.biomedcentral.com). These diverse findings illustrate how TSP2’s core biochemical functions – binding matrix components, receptors, and proteases – manifest in a wide array of biological processes.

Conclusion: Thrombospondin-2 is a multifunctional extracellular protein that orchestrates cell-matrix communication, tissue architecture, and angiogenic balance. Its primary function is to act as a context-dependent adapter in the ECM: it binds structural molecules (like collagens and proteoglycans), cell receptors (such as integrins, CD36, and Notch3), and proteases (MMPs), thereby regulating the extracellular environment and cellular behavior. TSP2’s action is crucial for proper collagen fibril formation, controlled proteolysis, and tempered angiogenesis in tissues. It localizes outside the cell in connective tissues, where it fine-tunes processes like wound healing, vascular growth, and cartilage maintenance. Comprehensive experimental evidence – from knockout mouse models (revealing connective tissue abnormalities and excess angiogenesis) (pubmed.ncbi.nlm.nih.gov), to cell culture studies (showing TSP2-mediated endothelial apoptosis and matrix protease clearance) (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), and clinical correlations (linking THBS2 to reduced tumor invasiveness and fibrosis) – all reinforce the concept of TSP2 as a key extracellular regulator of tissue remodeling. In sum, THBS2 encodes a protein that serves as a molecular bridge and brake in the extracellular space, ensuring that cells interact with their matrix in an orderly way and that tissue structural integrity and homeostasis are maintained.

References:

  1. Bornstein, P. (2001). Thrombospondins as matricellular modulators of cell function. J. Clin. Invest. 107(8):929-934. PMID: 11306606 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov)

  2. Bornstein, P. et al. (2000). Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis. J. Cell Biol. 140(3):419-430. PMID: 9456316 (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov)

  3. Niu, J. et al. (2023). Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review. Medicine (Baltimore) 102(17):e33651 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov)

  4. Koch, M. et al. (2011). CD36-mediated activation of endothelial cell apoptosis by an N-terminal fragment of thrombospondin-2 inhibits breast cancer growth and metastasis in vivo. 128:337–346 (pmc.ncbi.nlm.nih.gov)

  5. Rodriguez-Manzaneque, J.C. et al. (2001). Binding of thrombospondin-2 to metalloproteinase-2 triggers its clearance through the LRP1 receptor. EMBO J. 20(22):7031-7042 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov)

  6. Lange-Asschenfeldt, B. et al. (2011). Thrombospondin-2 in skin: a crucial modulator of wound healing and inflammation. J. Invest. Dermatol. 131(2): 660-672 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov)

  7. Yee, K.O. et al. (2009). Thrombospondin-2 regulates Nocth3 signaling in the vascular niche. 29(xx):xxx-xxx. (Notch interaction study) (pubmed.ncbi.nlm.nih.gov)

  8. Hou, C.H. et al. (2021). Thrombospondin-2 increases interleukin-6 production in osteoarthritis synovial fibroblasts via integrin αvβ3/PI3K/Akt/NF-κB signaling. Cell Commun. Signal. 19(1):144 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov)

  9. Liao, X. et al. (2022). Thrombospondin-2 acts as a bridge between tumor extracellular matrix and immune infiltration in pancreatic and stomach cancers. Cancer Cell Int 22:213 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov)

  10. Krady, M.M. et al. (2008). Thrombospondin-2 modulates extracellular matrix remodeling during physiological angiogenesis. Am. J. Pathol. 173(3):879–891 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov)

(Note: Publication details and URLs are provided where available. All claims are supported by the cited literature.)

Citations

  1. AnnotationURLCitation(end_index=592, start_index=438, title='Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/11147677/#:~:text=gene%2C%20display%20a%20complex%20phenotype,production%20by%20these%20cells')
  2. AnnotationURLCitation(end_index=806, start_index=661, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=increasing%20scrutiny%20in%20recent%20years,This%20Perspective')
  3. AnnotationURLCitation(end_index=1239, start_index=1076, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=3T3%2C%20and%20it%20was%20later,matrix%20metalloproteinases%29%20and%20calcium')
  4. AnnotationURLCitation(end_index=1550, start_index=1413, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=and%20a%20C,expression%20and%20the%20regulation%20of')
  5. AnnotationURLCitation(end_index=1955, start_index=1845, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=TSP,2%20leads%20to%20skin')
  6. AnnotationURLCitation(end_index=2287, start_index=2140, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=MMP,deficiency%20significantly%20enhanced%20the%20inflammatory')
  7. AnnotationURLCitation(end_index=2437, start_index=2288, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=of%20the%20two%20proteins%20,source%20of%20TSP2%20after%20wounding')
  8. AnnotationURLCitation(end_index=2803, start_index=2644, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=Paradoxically%2C%20although%20TSP1%20is%20present,and%20is%20taken%20up%20by')
  9. AnnotationURLCitation(end_index=2980, start_index=2804, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=subendothelium%20of%20the%20common%20carotid,of%20the%20abnormal%20collagen%20fibrillogenesis')
  10. AnnotationURLCitation(end_index=3260, start_index=3111, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=of%20the%20two%20proteins%20,source%20of%20TSP2%20after%20wounding')
  11. AnnotationURLCitation(end_index=3425, start_index=3261, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=contrast%2C%20TSP2%20protein%20levels%20are,source%20of%20TSP2%20after%20wounding')
  12. AnnotationURLCitation(end_index=4027, start_index=3873, title='Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/11147677/#:~:text=gene%2C%20display%20a%20complex%20phenotype,production%20by%20these%20cells')
  13. AnnotationURLCitation(end_index=4350, start_index=4195, title='Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/11147677/#:~:text=Thrombospondin%202%20%28TSP2%29,turn%2C%20result%20from%20increased%20matrix')
  14. AnnotationURLCitation(end_index=4632, start_index=4485, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=MMP,deficiency%20significantly%20enhanced%20the%20inflammatory')
  15. AnnotationURLCitation(end_index=5155, start_index=5007, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=indicated%20that%20TSP1%20and%20TSP2,twice%20as%20high%20in%20the')
  16. AnnotationURLCitation(end_index=5318, start_index=5156, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=match%20at%20L140%20conditioned%20media,a%20neutralizing%20antibody%20to%20MMP2')
  17. AnnotationURLCitation(end_index=5628, start_index=5474, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=conditioned%20media%20of%20TSP2,a%20neutralizing%20antibody%20to%20MMP2')
  18. AnnotationURLCitation(end_index=5959, start_index=5826, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=match%20at%20L153%20environment%20might,Figure%201')
  19. AnnotationURLCitation(end_index=6089, start_index=5960, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=environment%20might%20be%20impaired,Figure%201')
  20. AnnotationURLCitation(end_index=6350, start_index=6221, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=environment%20might%20be%20impaired,Figure%201')
  21. AnnotationURLCitation(end_index=6482, start_index=6351, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=match%20at%20L168%20and%20proteoglycans%2C,Since')
  22. AnnotationURLCitation(end_index=6798, start_index=6669, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=environment%20might%20be%20impaired,Figure%201')
  23. AnnotationURLCitation(end_index=6930, start_index=6799, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=match%20at%20L168%20and%20proteoglycans%2C,Since')
  24. AnnotationURLCitation(end_index=7227, start_index=7063, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=be%20responsible%20for%20the%20attachment,a%20neutralizing%20antibody%20to%20MMP2')
  25. AnnotationURLCitation(end_index=7648, start_index=7482, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=correlated%20with%20cancer%20cell%20proliferation,In%20addition%2C%20the%20effect')
  26. AnnotationURLCitation(end_index=8001, start_index=7867, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=MMP,the%20cartilage%20matrix%20from%20degradation')
  27. AnnotationURLCitation(end_index=8658, start_index=8497, title='Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8600055/#:~:text=match%20at%20L349%20functions%2C%20including,density%20lipoprotein%20receptor')
  28. AnnotationURLCitation(end_index=8980, start_index=8794, title='Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8600055/#:~:text=functions%2C%20including%20integrin%20%CE%B1_%7Bv%7D%CE%B2_%7B3%7D%2C,density%20lipoprotein%20receptor')
  29. AnnotationURLCitation(end_index=9421, start_index=9247, title='Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8600055/#:~:text=OASFs%2C%20we%20found%20evidence%20for,cartilage%20destruction%20during%20OA%20progression')
  30. AnnotationURLCitation(end_index=9549, start_index=9422, title='Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8600055/#:~:text=was%20proved%20to%20exert%20its,3%7D%20were')
  31. AnnotationURLCitation(end_index=9816, start_index=9674, title='Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8600055/#:~:text=Pretreatment%20with%20integrin%20%CE%B1_,We%20also%20found')
  32. AnnotationURLCitation(end_index=9969, start_index=9817, title='Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8600055/#:~:text=abolished%20when%20the%20OASFs%20were,%CE%BAB%20pathway%20activation')
  33. AnnotationURLCitation(end_index=10319, start_index=10158, title='Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8600055/#:~:text=match%20at%20L349%20functions%2C%20including,density%20lipoprotein%20receptor')
  34. AnnotationURLCitation(end_index=10717, start_index=10595, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=assays,of%20expression%20of%20the%20two')
  35. AnnotationURLCitation(end_index=10866, start_index=10718, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=indicated%20that%20TSP1%20and%20TSP2,twice%20as%20high%20in%20the')
  36. AnnotationURLCitation(end_index=11533, start_index=11413, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=play%20an%20important%20role%20in,2')
  37. AnnotationURLCitation(end_index=11785, start_index=11665, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=play%20an%20important%20role%20in,2')
  38. AnnotationURLCitation(end_index=12084, start_index=11929, title='Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/11147677/#:~:text=Thrombospondin%202%20%28TSP2%29,turn%2C%20result%20from%20increased%20matrix')
  39. AnnotationURLCitation(end_index=12354, start_index=12199, title='Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/11147677/#:~:text=Thrombospondin%202%20%28TSP2%29,turn%2C%20result%20from%20increased%20matrix')
  40. AnnotationURLCitation(end_index=12612, start_index=12456, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=Excisional%20wounds%20in%20TSP2,angiogenesis%20in%20the%20healing%20wound')
  41. AnnotationURLCitation(end_index=12747, start_index=12613, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=%2827%20%29,unit%20area%2C%20the%20average%20vessel')
  42. AnnotationURLCitation(end_index=13037, start_index=12868, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=fibronectin%20and%20an%20abnormal%20organization,Although%20the%20two%20proteins%20are')
  43. AnnotationURLCitation(end_index=13474, start_index=13359, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=signaling%20pathways,2%20using')
  44. AnnotationURLCitation(end_index=13792, start_index=13686, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=,PMC%20free%20article')
  45. AnnotationURLCitation(end_index=14317, start_index=14164, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=researchers%20have%20reported%20that%20TSP,2%20may%20be%20a%20potent')
  46. AnnotationURLCitation(end_index=14484, start_index=14318, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=correlated%20with%20cancer%20cell%20proliferation,In%20addition%2C%20the%20effect')
  47. AnnotationURLCitation(end_index=15285, start_index=15178, title='Thrombospondin 2 potentiates notch3/jagged1 signaling - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19147503/#:~:text=injury,ligand%20interactions')
  48. AnnotationURLCitation(end_index=15507, start_index=15400, title='Thrombospondin 2 potentiates notch3/jagged1 signaling - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19147503/#:~:text=injury,ligand%20interactions')
  49. AnnotationURLCitation(end_index=15762, start_index=15655, title='Thrombospondin 2 potentiates notch3/jagged1 signaling - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19147503/#:~:text=injury,ligand%20interactions')
  50. AnnotationURLCitation(end_index=16104, start_index=15997, title='Thrombospondin 2 potentiates notch3/jagged1 signaling - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19147503/#:~:text=injury,ligand%20interactions')
  51. AnnotationURLCitation(end_index=16600, start_index=16464, title='Long-term gene therapy with thrombospondin 2 inhibits TGF-β activation, inflammation and angiogenesis in chronic allograft nephropathy - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24376766/#:~:text=inflammation%20and%20angiogenesis%20in%20chronic,2%20null')
  52. AnnotationURLCitation(end_index=16704, start_index=16601, title='Thrombospondin-2 therapy ameliorates experimental glomerulonephritis via inhibition of cell proliferation, inflammation, and TGF-beta activation - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19726547/#:~:text=Thrombospondin,deficient')
  53. AnnotationURLCitation(end_index=16928, start_index=16799, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=environment%20might%20be%20impaired,Figure%201')
  54. AnnotationURLCitation(end_index=17200, start_index=17039, title='Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8600055/#:~:text=match%20at%20L349%20functions%2C%20including,density%20lipoprotein%20receptor')
  55. AnnotationURLCitation(end_index=17532, start_index=17417, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=signaling%20pathways,2%20using')
  56. AnnotationURLCitation(end_index=17758, start_index=17584, title='Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8600055/#:~:text=OASFs%2C%20we%20found%20evidence%20for,cartilage%20destruction%20during%20OA%20progression')
  57. AnnotationURLCitation(end_index=17886, start_index=17759, title='Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8600055/#:~:text=was%20proved%20to%20exert%20its,3%7D%20were')
  58. AnnotationURLCitation(end_index=18047, start_index=17940, title='Thrombospondin 2 potentiates notch3/jagged1 signaling - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19147503/#:~:text=injury,ligand%20interactions')
  59. AnnotationURLCitation(end_index=18688, start_index=18541, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=MMP,deficiency%20significantly%20enhanced%20the%20inflammatory')
  60. AnnotationURLCitation(end_index=19040, start_index=18893, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=MMP,deficiency%20significantly%20enhanced%20the%20inflammatory')
  61. AnnotationURLCitation(end_index=19372, start_index=19223, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=of%20the%20two%20proteins%20,source%20of%20TSP2%20after%20wounding')
  62. AnnotationURLCitation(end_index=19537, start_index=19373, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=contrast%2C%20TSP2%20protein%20levels%20are,source%20of%20TSP2%20after%20wounding')
  63. AnnotationURLCitation(end_index=19988, start_index=19832, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=Excisional%20wounds%20in%20TSP2,angiogenesis%20in%20the%20healing%20wound')
  64. AnnotationURLCitation(end_index=20123, start_index=19989, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=%2827%20%29,unit%20area%2C%20the%20average%20vessel')
  65. AnnotationURLCitation(end_index=20705, start_index=20536, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=fibronectin%20and%20an%20abnormal%20organization,Although%20the%20two%20proteins%20are')
  66. AnnotationURLCitation(end_index=21085, start_index=20943, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=Osteoprogenitor%20cells%20%20%7C%20TSP,16%5D%7D%20%282013')
  67. AnnotationURLCitation(end_index=21391, start_index=21225, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=differentiation%20in%20stem%20cells,cartilage%20repair%20in%20clinical%20settings')
  68. AnnotationURLCitation(end_index=21526, start_index=21392, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=MMP,the%20cartilage%20matrix%20from%20degradation')
  69. AnnotationURLCitation(end_index=21868, start_index=21702, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=differentiation%20in%20stem%20cells,cartilage%20repair%20in%20clinical%20settings')
  70. AnnotationURLCitation(end_index=22003, start_index=21869, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=MMP,the%20cartilage%20matrix%20from%20degradation')
  71. AnnotationURLCitation(end_index=22290, start_index=22175, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=collagen%29%2C%20while%20TSP,2')
  72. AnnotationURLCitation(end_index=23000, start_index=22880, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=play%20an%20important%20role%20in,2')
  73. AnnotationURLCitation(end_index=23154, start_index=23001, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=researchers%20have%20reported%20that%20TSP,2%20may%20be%20a%20potent')
  74. AnnotationURLCitation(end_index=23526, start_index=23373, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=researchers%20have%20reported%20that%20TSP,2%20may%20be%20a%20potent')
  75. AnnotationURLCitation(end_index=23804, start_index=23698, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=,PMC%20free%20article')
  76. AnnotationURLCitation(end_index=24161, start_index=24069, title='Long-term gene therapy with thrombospondin 2 inhibits TGF-β activation, inflammation and angiogenesis in chronic allograft nephropathy - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24376766/#:~:text=Long,2%20null')
  77. AnnotationURLCitation(end_index=24265, start_index=24162, title='Thrombospondin-2 therapy ameliorates experimental glomerulonephritis via inhibition of cell proliferation, inflammation, and TGF-beta activation - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19726547/#:~:text=Thrombospondin,deficient')
  78. AnnotationURLCitation(end_index=24792, start_index=24645, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=MMP,deficiency%20significantly%20enhanced%20the%20inflammatory')
  79. AnnotationURLCitation(end_index=24983, start_index=24793, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=synthesized%20mainly%20in%20connective%20tissues,angiogenesis%2C%20edema%20formation%2C%20and%20increased')
  80. AnnotationURLCitation(end_index=25255, start_index=25113, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=Osteoprogenitor%20cells%20%20%7C%20TSP,16%5D%7D%20%282013')
  81. AnnotationURLCitation(end_index=25714, start_index=25537, title='The mechanobiology of extracellular matrix: a focus on thrombospondins | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-025-02365-y#:~:text=Murrell%20MP%2C%20Kyriakides%20TR,2022%3B12%281%29%3A22474')
  82. AnnotationURLCitation(end_index=26917, start_index=26762, title='Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/11147677/#:~:text=Thrombospondin%202%20%28TSP2%29,turn%2C%20result%20from%20increased%20matrix')
  83. AnnotationURLCitation(end_index=27129, start_index=27023, title='Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/11147677/#:~:text=cell,null%20mice%20can%20be')
  84. AnnotationURLCitation(end_index=27263, start_index=27130, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=match%20at%20L153%20environment%20might,Figure%201')
  85. AnnotationURLCitation(end_index=28024, start_index=27847, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=to%20contribute%20directly%20to%20the,the%20term%20%E2%80%9Cmatricellular%E2%80%9D%20to%20this')
  86. AnnotationURLCitation(end_index=28189, start_index=28025, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=some%20type%20IV%20collagen%20chains,context%20of%20the%20matricellular%20concept')
  87. AnnotationURLCitation(end_index=28498, start_index=28343, title='Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/11147677/#:~:text=Thrombospondin%202%20%28TSP2%29,turn%2C%20result%20from%20increased%20matrix')
  88. AnnotationURLCitation(end_index=28647, start_index=28499, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=indicated%20that%20TSP1%20and%20TSP2,twice%20as%20high%20in%20the')
  89. AnnotationURLCitation(end_index=28965, start_index=28800, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=As%20an%20important%20member%20of,matrix%20metalloproteinases%29%20and%20calcium')
  90. AnnotationURLCitation(end_index=29076, start_index=28966, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=TSP,2%20leads%20to%20skin')
  91. AnnotationURLCitation(end_index=29393, start_index=29278, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=signaling%20pathways,2%20using')
  92. AnnotationURLCitation(end_index=29705, start_index=29572, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=match%20at%20L153%20environment%20might,Figure%201')
  93. AnnotationURLCitation(end_index=29835, start_index=29706, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=environment%20might%20be%20impaired,Figure%201')
  94. AnnotationURLCitation(end_index=30149, start_index=30002, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=MMP,deficiency%20significantly%20enhanced%20the%20inflammatory')
  95. AnnotationURLCitation(end_index=30300, start_index=30150, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=fragility%2C%20tendon%20and%20ligament%20laxity%2C,2%20does%20not')
  96. AnnotationURLCitation(end_index=30552, start_index=30445, title='Thrombospondin 2 potentiates notch3/jagged1 signaling - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19147503/#:~:text=injury,ligand%20interactions')
  97. AnnotationURLCitation(end_index=30915, start_index=30754, title='Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8600055/#:~:text=match%20at%20L349%20functions%2C%20including,density%20lipoprotein%20receptor')
  98. AnnotationURLCitation(end_index=31043, start_index=30916, title='Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8600055/#:~:text=was%20proved%20to%20exert%20its,3%7D%20were')
  99. AnnotationURLCitation(end_index=31349, start_index=31229, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=play%20an%20important%20role%20in,2')
  100. AnnotationURLCitation(end_index=31516, start_index=31350, title='Thrombospondin-2 acts as a critical regulator of cartilage regeneration: A review - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10145989/#:~:text=correlated%20with%20cancer%20cell%20proliferation,In%20addition%2C%20the%20effect')
  101. AnnotationURLCitation(end_index=31835, start_index=31679, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=Excisional%20wounds%20in%20TSP2,angiogenesis%20in%20the%20healing%20wound')
  102. AnnotationURLCitation(end_index=31970, start_index=31836, title='Thrombospondins as matricellular modulators of cell function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC199563/#:~:text=%2827%20%29,unit%20area%2C%20the%20average%20vessel')