{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n C‐Type Lectin Domain Family 3 Member B (CLEC3B), which encodes the secreted protein tetranectin, plays multifaceted roles in tissue remodeling and homeostasis. Functionally, CLEC3B/tetranectin is well recognized for its ability to bind plasminogen and enhance tissue plasminogen activator–mediated plasminogen activation, a property that is thought to facilitate extracellular matrix turnover and remodeling processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In models of musculoskeletal repair, loss of tetranectin delays fracture healing and impairs normal callus formation, underscoring its positive regulatory role in osteogenesis and bone regeneration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In the context of degenerative joint disease, integrated analyses have revealed that CLEC3B is differentially regulated at the epigenetic, transcript, and protein levels during osteoarthritis progression, implicating it as a potential marker of disease evolution."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In oncology, emerging evidence indicates that CLEC3B is downregulated in several tumor types. In hepatocellular carcinoma, low serum and tumor expression levels of CLEC3B are significantly linked to enhanced migration, invasion, epithelial–mesenchymal transition, and poorer prognosis, effects that appear to be mediated through modulation of VEGF secretion via the AMPK pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Consistent with these findings, analysis in clear cell renal cell carcinoma revealed frequent copy number loss of CLEC3B, with its downregulation being associated with tumor progression and a more aggressive, high‐proliferation phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, in ovarian cancer, serum tetranectin levels have been identified as independent prognostic factors, reinforcing its potential utility as a biomarker for tumor aggressiveness and patient outcome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in tissue repair and tumorigenesis, genetic studies have implicated CLEC3B in systemic conditions related to aging. A missense variant in CLEC3B (p.S106G) has been robustly associated with extreme longevity in Asian populations"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", although subsequent analyses in Caucasian cohorts did not replicate this association."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, investigations in cardiomyocytes have demonstrated that CLEC3B exerts cardioprotective effects under hypoxic conditions by activating the PI3K/Akt pathway and reducing apoptosis, suggesting a role in mitigating ischemic injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CLEC3B/tetranectin is emerging as a multifunctional protein involved in extracellular proteolysis, anabolic processes in bone and cartilage, modulation of angiogenesis, and the regulation of tumor progression, while also representing a potential biomarker for both cancer prognosis and cardiovascular/neurodegenerative conditions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Uffe B Westergaard, Mikkel H Andersen, Christian W Heegaard, et al. 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