Table 1.
Functional and pathological implications of MMP regulation in OA
| Regulatory factor | Direct/indirect target of MMP-13 | Effect on MMP-13 | Function in OA onset/progression |
|---|---|---|---|
| LRP1 [17] | Directly binds to MMP-13 | Endocytosed and degraded MMP-13 | Inhibits OA onset |
| leptin [29] | Direct | Activate MMP-13 | Promotes OA onset |
| HTRA1 [30] | Indirect/DDR2 | Upregulate MMP-13 | Promotes OA onset |
| LEF1/ELF3/HIF2α/Runx2/CEBPβ [34, 35] | Directly binds to promoter | Upregulate MMP-13 | Promotes OA onset |
| HMW-HA [36, 37] | Indirect | Inhibits production of MMP-13 | Inhibits OA onset |
| miR-9 [41] | Targets MMP-13 | Inhibits production of MMP-13 | Promotes progression of late-stage OA |
| miR-146a [42–45] | Targets MMP-13 | Inhibits production of MMP-13 | Promotes OA onset |
| miR-127-5p [20] | Targets MMP-13 | Inhibits production of MMP-13 | Inhibits OA progression |
| miR-27b [46] | Targets MMP-13 | Inhibits production of MMP-13 | Inhibits OA progression |
| miR-320 [47] | Targets MMP-13 | Inhibits production of MMP-13 | Inhibits OA progression |
| miR-136 [61] | Targets MMP-13 | Inhibits production of MMP-13 | Inhibits OA progression |
| miR-27a [48] | Indirect | Inhibits production of MMP-13 | A slight decrease in OA |
| miR-140 [48] | Indirect/IGFBP-5 | Inhibits production of MMP-13 | Inhibits OA progression |
| Indirect/ER binding miR-140 promoter | Inhibits production of MMP-13 | Inhibits OA progression | |
| miR-488 [49] | Indirect/ZIP-8 | Inhibits MMP-13 activity | Inhibits OA progression |
| miR-24 [15] | Indirect | Inhibits production of MMP-13 | Inhibits OA progression |
| miRNA-148a [50] | Indirect | Inhibits production of MMP-13 | Inhibits chondrocyte hypertrophy |
| miR-222 [51] | Indirect/HDAC-4 | Inhibits production of MMP-13 | Inhibits OA onset |
| miR-22 [52] | Indirect/BMP-7, PPARα | Activates MMP-13 | Promotes OA progression |
| miR-181b [53] | Indirect | Increases production of MMP-13 | Promotes OA progression |
| miR-33a [54] | Indirect | Increases production of MMP-13 | Promotes OA progression |
| miR-145 [55] | Indirect/Sox9 | Increases production of MMP-13 | Promotes OA progression |
| miR-483 [56] | Indirect/BMP-7, TGF-β | Increases production of MMP-13 | Promotes OA onset |
| LncRNA-CIR [59] | Indirect | Increases production of MMP-13 | Promotes OA onset and progression |
| GAS5 [60] | Indirect/miR-21 | Increases production of MMP-13 | Promotes OA progression |
| circRNA-CER [61] | Competes with miR-136 as a ‘sponge’ | Up-regulation of MMP-13 | Promotes OA progression |