Table 1.

Summary of miRNAs which are differentially expressed in OA.

microRNA	Functional Effect of Increased/Decreased miRNA Expression	Ref.
miR-16 ↑	inhibition of FGFR by targeting SMAD3, altered proliferation and increased apoptosis, TGF-β signaling pathway affected	[71]
miR-21 ↑	inhibition of GDF-5 expression	[72]
miR-23a ↑	inhibition of FGFR by targeting SMAD3, altered proliferation and increased apoptosis, TGF-β signaling pathway affected	[71]
miR-25 ↑	WFA-induced upregulation of COX-2 expression, mediation of inflammatory responses in chondrocytes	[73]
miR-27b ↑	suppression of RC3H1 and QKI in OA synovium	[74]
miR-29b ↑	induction of chondrocyte apoptosis by targeting progranulin	[75]
miR-30b ↑	cartilage matrix degradation by targeting SOX9, ADAMTS-5 and ERG	[71]
miR-30c ↑	cartilage matrix degradation by targeting SOX9, ADAMTS-5 and ERG	[71]
miR-33a ↑	upregulation of MMP-13 and ECM degradation, regulation of cholesterol synthesis in TGF-β1/Akt/SREBP-2 pathway and cholesterol efflux-related ApoA1 and ABCA1	[76]
miR-34b ↑	modulation of OA chondrocyte proliferation by targeting CYR61, which inhibits ADAMTS-4 induced aggrecan degradation in cartilage	[73]
miR-104 ↑	unknown	[73]
miR-122a ↑	unknown	[73]
miR-126 ↑	unknown	[71]
miR-128a ↑	repression of chondrocyte autophagy by targeting Atg12	[77]
miR-130a ↑	sponging effect by aberrantly highly expressed HOTAIR lncRNA, massive apoptosis events, suppression of autophagy in chondrocytes	[78]
miR-133a ↑	inhibition of synovium pain-related genes, especially DST and TBXAS1	[79]
miR-135a ↑	unknown	[73]
miR-135b ↑	unknown	[73]
miR-139 ↑	inhibition of MCPIP1, activation of IL-6 and apoptosis	[73]
miR-144 ↑	unknown	[73]
miR-145 ↑	attenuation of TNF-α-driven cartilage matrix degradation by direct suppression of MKK4	[80]
miR-146a ↑	targeting SMAD4 disturbing TGF-β pathway, increased apoptosis, upregulation of VEGF	[81,82,83]
miR-147 ↑	unknown	[74]
miR-181a ↑	inhibition of chondrocytes proliferation and induction of apoptosis by targeting PTEN	[84]
miR-181b ↑	articular cartilage degeneration, destruction of lumbar facet joint cartilage	[85]
miR-184 ↑	unknown	[71]
miR-186 ↑	unknown	[71]
miR-200a ↑	unknown	[73]
miR-211 ↑	unknown	[73]
miR-215 ↑	inhibition of synovium pain-related genes, especially DST and TBXAS1	[86]
miR-218 ↑	inhibition the PI3K/Akt/mTOR signaling pathway, cartilage destruction	[87]
miR-224 ↑	inhibition of synovium pain-related genes, especially DST and TBXAS1	[86]
miR-299 ↑	unknown	[73]
miR-335 ↑	inhibition of synovium pain-related genes, especially DST and TBXAS1	[86]
miR-345 ↑	unknown	[71]
miR-365 ↑	upregulated expression of catabolic COL10A1 and MMP-13 by targeting HDAC4, activation of IL-6 and apoptosis	[88]
miR-381 ↑	upregulation of MMP13 and RUNX2 expression via targeting of HDAC4 cartilage degeneration	[89]
miR-455 ↑	regulating TGF-β signalling by suppression of the Smad2/3 pathway, targeting ACVR2B, SMAD2, CHRDL1	[90]
miR-486 ↑	inhibition of chondrocyte proliferation and migration by suppressing SMAD2 gene	[91]
miR-885 ↑	unknown	[71]
miR-9 ↓	increased chondrocytes proliferation and inhibition of cell apoptosis by targeting NF-κB	[92]
miR-26 ↓	induction of NF-κB signaling pathway	[93]
miR-27b ↓	inhibition of MMP-13	[94]
miR-29a ↓	inhibition of SMAD3, NFκB and WNT signaling pathway, part of ECM remodeling machinery	[71]
miR-107 ↓	unknown	[73]
miR-125b ↓	ADAMTS-4 - induced aggrecan degradation in cartilage	[95]
miR-127 ↓	decreased ECM synthesis by targeting IL-1β induced MMP-13	[96]
miR-140 ↓	targeting IGFR, ADAMTS5, MMP-13, IGFBP5 and RALA cartilage development and homeostasis, development of age-related OA-like changes	[97,98,99,100,101]
miR-148a ↓	targeting COL10A1, MMP13 and ADAMTS5, inhibition of hypertrophic differentiation, production and deposition of type II collagen and proteoglycan retention	[102]
miR-149 ↓	upregulation of TNFα, IL1β and IL6, activation of inflammation by targeting TNFα	[73,103]
miR-210 ↓	inhibition of NF-κB signaling pathway by targeting DR6 increasing inflammation	[104]
miR-221 ↓	activation of expression of catabolic genes, degeneration of cartilage tissues by upregulated expression of SDF1	[105]
miR-483 ↓	upregulation of catabolic genes expression, inhibition of TGF-β signaling pathway	[71]
miR-488 ↓	upregulation of catabolic genes expression by targeting ZIP8	[106]
miR-558 ↓	inhibition of COX-2 expression, inhibition of IL-1β-stimulated catabolic effect, altered inhibition of inflammatory factors	[107]

↑—upregulated, ↓—downregulated. FGFR—fibroblast growth factor receptor, SMAD3—mothers against decapentaplegic homolog 3, TGF-β—transforming growth factor β, GDF-5—growth differentiation factor 5, WFA—Wisteria floribunda lectin, COX-2—cyclooxygenase-2, RC3H1—ring finger and CCCH-type domains 1, QKI—Quaking, NFκB—nuclear factor kappa-light-chain-enhancer of activated B cells, SOX9—SRY-box transcription factor 9, ADAMTS-5—a disintegrin and metalloproteinase with thrombospondin type 1 motif 5, ERG—ETS transcription factor ERG, MMP-13—matrix metallopeptidase 13, ECM—extracellular matrix, CYR61—cysteine rich angiogenic inducer 61, Atg12—autophagy related 12, DST—dystonin, TBXAS1—thromboxane A synthase 1, MCPIP1—monocyte chemoattractant protein-induced protein 1, IL-6—interleukin 6, TNF-α—tumor necrosis factor alpha-like, MKK4—mitogen-activated protein kinase kinase 4, VEGF—vascular endothelial growth factor, PTEN—phosphatase and tensin homolog, COL10A1—collagen type X alpha 1 chain, HDAC4—histone deacetylase 4, RUNX2—RUNX family transcription factor 2; runt-related transcription factor 2, ACVR2B—activin A receptor type 2B, SMAD2—SMAD family member 2; small mothers against decapentaplegic homolog 2, CHRDL1—chordin like 1, RALA—Ras-related protein Ral-A, DR6—death receptor 6, SDF1—stromal cell-derived factor 1, ZIP8—zinc transporter 8,.