| Area | Key finding | Evidence type (review/primary/preprint) | Quantitative details (sample sizes, p-values, effect sizes) | Source (authors, journal, year) | URL |
|---|---|---|---|---|---|
| Protein identity/structure | Human THBS3 is a thrombospondin family matricellular/extracellular glycoprotein in Group B; Group B thrombospondins are pentameric extracellular calcium-binding proteins with multimeric architecture for ECM and cell-surface interactions. | Review | No THBS3-specific effect size reported in the cited snippet. (pqac-00000005) | Pan et al., *Frontiers in Cardiovascular Medicine*, 2024 | https://doi.org/10.3389/fcvm.2024.1337586 |
| Protein identity/structure | TSP3 is a pentamer formed via amino-terminal disulfide bonding; its conserved C-terminal region contains a calcium-binding signature domain, consistent with ECM-localized matricellular function. (pqac-00000007) | Review | No quantitative statistics in the cited snippet. | Alford & Hankenson, *Seminars in Cell & Developmental Biology*, 2024 | https://doi.org/10.1016/j.semcdb.2023.06.011 |
| Protein identity/structure | Structural review evidence indicates Group B thrombospondins (including THBS3) differ from Group A by lacking an N-terminal module, adding an EGF-like repeat, lacking an N-glycosylation site in wire repeat 1C, and carrying insertions in wire repeat 11C/C-terminus. (pqac-00000006) | Review | No quantitative statistics in the cited snippet. | Carlson et al., *Cellular and Molecular Life Sciences*, 2008 | https://doi.org/10.1007/s00018-007-7484-1 |
| Skeletal/cartilage biology | In skeletal development, TSP3 expression is localized to the growth plate proliferating zone and perichondrium; all five TSPs are present in articular cartilage. (pqac-00000004, pqac-00000015, pqac-00000017) | Review | No quantitative statistics in the cited snippets. | Alford & Hankenson, *Seminars in Cell & Developmental Biology*, 2024 | https://doi.org/10.1016/j.semcdb.2023.06.011 |
| Skeletal/cartilage biology | Mouse loss-of-function data summarized in review indicate TSP3 knockout causes accelerated ossification of the femoral head and transient increases in cortical moment of inertia that increase femur bending strength; combinatorial knockouts with TSP3 worsen growth plate disorganization and shorten limbs. (pqac-00000004, pqac-00000015) | Review | No p-values reported in the cited snippets. | Alford & Hankenson, *Seminars in Cell & Developmental Biology*, 2024 | https://doi.org/10.1016/j.semcdb.2023.06.011 |
| Osteoarthritis mechanism | THBS3 is upregulated in osteoarthritic cartilage and OA chondrocytes versus healthy controls. (pqac-00000001, pqac-00000002, pqac-00000003) | Preprint primary study | Human cartilage n=10; Western blot p=0.0236; RT-qPCR p=0.0002. (pqac-00000002) | Yan et al., Research Square preprint, 2024 | https://doi.org/10.21203/rs.3.rs-4167008/v1 |
| Osteoarthritis mechanism | Recombinant THBS3 increased catabolic enzymes (MMP-13, ADAMTS-5), suppressed Aggrecan, and promoted endothelial migration/tube formation relevant to cartilage vascularization/osteogenesis coupling in OA models. (pqac-00000002) | Preprint primary study | IL-1β induced THBS3 in normal chondrocytes: p=0.0138; THBS3 siRNA reduced THBS3: p<0.0001; HUVEC migration maximal at 100 nM: p=0.0040; tube formation at 50 nM: p=0.0036 and 100 nM: p<0.0001; mouse CIOA model n=18 total, groups of 6. | Yan et al., Research Square preprint, 2024 | https://doi.org/10.21203/rs.3.rs-4167008/v1 |
| Osteoarthritis mechanism | THBS3 was linked to TGF-β/Smad2/3 signaling in OA; THBS3 increased chondrocyte TGF-β expression and TGF-β pathway inhibition blunted THBS3-induced pro-angiogenic/pro-osteogenic factors. (pqac-00000000, pqac-00000003) | Preprint primary study | TGF-β expression peak at 6 h: p=0.0353; p-SMAD2/3 changes: p=0.0004 and p<0.0001; additional TGF-β inhibitor effect p=0.0070; inhibition of BMP-2/FGF-2/ANG-2/VEGF-A/PDGF-B induction p range 0.0276–0.0052. | Yan et al., Research Square preprint, 2024 | https://doi.org/10.21203/rs.3.rs-4167008/v1 |
| Viral entry/coreceptor | THBS3 functions as a pseudorabies virus (PRV) coreceptor/host factor; knockdown, knockout, antibody blocking, and soluble protein assays all reduced infection. (pqac-00000010, pqac-00000011) | Primary study | siRNA knockdown reduced PRV-GFP infection by 68.4% (PK15), 54.9% (ST), 62.8% (N2a); second siRNA inhibited infection by 71.7%; CRISPR knockout reduced infection by ~80%; overexpression nearly tripled infection; blocking antibody effective at 40 mg/mL. | Pan et al., *Journal of Virology*, 2023 | https://doi.org/10.1128/jvi.01871-22 |
| Viral entry/coreceptor | THBS3 directly binds PRV glycoprotein D through its N- and C-terminal regions and promotes binding/fusion/entry; soluble THBS3 neutralized infectivity in a dose-dependent manner. (pqac-00000009, pqac-00000012) | Primary study | Overexpression increased virus binding up to 7.16-fold in CHO-K1 cells; knockdown reduced binding by ~50%; knockout reduced attachment by ~80%; soluble THBS3 at 400 µg/mL reduced infectivity by 60%. | Pan et al., *Journal of Virology*, 2023 | https://doi.org/10.1128/jvi.01871-22 |
| Human genetics | SMR analysis prioritized THBS3 as a significant pleiotropic gene for gout; higher blood THBS3 expression was associated with reduced gout risk. (pqac-00000008, pqac-00000013) | Primary study | eQTLGen blood cis-eQTL n=31,684; FinnGen gout GWAS n=272,412; top SNP rs760077; Beta = -0.202; P_SMR = 4.16 × 10^-13; HEIDI P = 0.219; FDR = 2.92 × 10^-9. | Wang et al., *Frontiers in Genetics*, 2024 | https://doi.org/10.3389/fgene.2024.1426860 |
| Cardiovascular/proteomics biomarker | A 2024 cardiovascular review states TSP3 is structurally similar to TSP4, can bind ATF6α to activate ER stress, and may worsen cardiac pathology by inhibiting intracellular integrin signaling and disrupting myocardial membrane stability; its role in NO signaling and immune-cell actions remains unclear. (pqac-00000018) | Review | No quantitative statistics in the cited snippet. | Pan et al., *Frontiers in Cardiovascular Medicine*, 2024 | https://doi.org/10.3389/fcvm.2024.1337586 |
| Cardiovascular/proteomics biomarker | In thoracic aortic aneurysm associated with bicuspid aortic valve, THBS3 was among proteins highlighted as altered in VSMCs/plasma and proposed as a stress-related plasma marker. (pqac-00000016, pqac-00000020, pqac-00000021) | Primary study | The cited snippets report altered abundance but do not provide THBS3-specific fold-changes, AUCs, or cutoffs. | Martin-Blazquez et al., *Journal of Proteome Research*, 2024 | https://doi.org/10.1021/acs.jproteome.3c00649 |


*Table: This table summarizes directly supported THBS3 findings gathered in this run, spanning protein identity, skeletal/cartilage biology, osteoarthritis, viral entry, human genetics, and cardiovascular biomarker evidence. It is useful as a citation-ready evidence map for building the full research report.*