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Table 1 Functional and pathological implications of MMP regulation in OA

From: New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis

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 [42,43,44,45] 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