Table 2.
Fibrogenic factors in OA.
| Protein (encoding gene) | Risk factors | Function | Notes | References |
|---|---|---|---|---|
| TGF-β and TGFβR | Aging | Receptors and ligands, signaling | Senescence-associated secretory phenotype | (41) |
| Hypoxia | Positive feedback cycle between NLRP3 inflammasome activation and TGF-β1 induction | (42) | ||
| ECM changes | Promotion of terminal differentiation of fibroblasts and the secretion of ECM components | (43) | ||
| Mechanical stress | activation and release of TGF-β1 | (44) | ||
| VEGF (VEGF) | Hypoxia | Growth factor | Modulated by HIF-1α at transcriptional level | (45) |
| IGF2 (IGF) | Hypoxia | Growth factor | Modulated by HIF-1α at transcriptional level | (45) |
| Angiotensin II | Hypoxia | Signaling | Modulated by HIF-2α at transcriptional level | (45) |
| NLRP3 | Hypoxia | Signaling | Positive feedback cycle between NLRP3 inflammasome activation and TGF-β1 induction | (42) |
| IL-1β | Hypoxia | Cytokine | Increases TGF-β1 induction | (42) |
| LOXs and LOXL | ECM changes | Amine oxidases and LOX like proteins | Regulation of phosphorylation of Smad2/3 or p65 orERK1/2 | (46–48) |
| LH2 (PLOD2) | ECM changes | Protease | PI3K/Akt signaling transduction; regulated by HIF or TGF | (49, 50) |
| CTGF | ECM changes | Growth factor | Reduction of Smad7 and promotion of TGF-β signaling | (51) |