Expression of miR-206 in Human Knee Articular Chondrocytes and Effects of miR-206 on Proliferation and Apoptosis of Articular Chondrocytes.

Increasing evidence has demonstrated that microRNAs regulate the development of cartilage and osteogenesis. Whether miR-206 participates in the development of human articular cartilage remains largely unknown. This study aimed to investigate the role of miR-206 in human chondrocytes. Expression of miR-206 was initially assessed in human osteoarthritis (OA) tissues and articular chondrocytes through quantitative real-time polymerase chain reaction. The effects of miR-206 on proliferation and apoptosis of human chondrocytes were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining assay. Then, the effects of miR-206 on type II collagen alpha 1 (Col2a1), aggrecan, runt-related transcription factor 2 (RUNX2) and matrix metalloproteinase13 (MMP13) were examined with quantitative real-time polymerase chain reaction and Western blot analysis. MiR-206 was significantly increased in human OA tissues and chondrocytes. MiR-206 significantly inhibited the proliferation of chondrocytes, but promoted apoptosis. Expression of Col2a1 and aggrecan were dramatically decreased, and the expression of RUNX2 and MMP13 were significantly increased when miR-206 was overexpressed. MiR-206 may participate in cartilage degradation in OA. Manipulation of the expression of miR-206 in human chondrocytes may be a novel therapeutic strategy for the treatment of OA.

Ni Z ，Shang X ，Tang G ，Niu L ... -  《-》

MicroRNA-483-5p Modulates the Expression of Cartilage-Related Genes in Human Chondrocytes through Down-Regulating TGF-β1 Expression.

Xu R ，Li J ，Wei B ，Huo W ，Wang L ... -  《-》

miR-105/Runx2 axis mediates FGF2-induced ADAMTS expression in osteoarthritis cartilage.

Ji Q ，Xu X ，Xu Y ，Fan Z ，Kang L ，Li L ，Liang Y ，Guo J ，Hong T ，Li Z ，Zhang Q ，Ye Q ，Wang Y ... -  《-》

Overexpression of hsa-miR-148a promotes cartilage production and inhibits cartilage degradation by osteoarthritic chondrocytes.

Hsa-miR-148a expression is decreased in Osteoarthritis (OA) cartilage, but its functional role in cartilage has never been studied. Therefore, our aim was to investigate the effects of overexpressing hsa-miR-148a on cartilage metabolism of OA chondrocytes. OA chondrocytes were transfected with a miRNA precursor for hsa-miR-148a or a miRNA precursor negative control. After 3, 7, 14 and 21 days, real-time PCR was performed to examine gene expression levels of aggrecan (ACAN), type I, II, and X collagen (COL1A1, COL2A1, COl10A1), matrix metallopeptidase 13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and the serpin peptidase inhibitor, clade H (heat shock protein 47), member 1 (SERPINH1). After 3 weeks, DNA content and proteoglycan and collagen content and release were determined. Type II collagen was analyzed at the protein level by Western blot. Overexpression of hsa-miR-148a had no effect on ACAN, COL1A1 and SERPINH1 gene expression, but increased COL2A1 and decreased COL10A1, MMP13 and ADAMTS5 gene expression. Luciferase reporter assay confirmed direct interaction of miR-148a and COL10A1, MMP13 and ADAMTS5. The matrix deposited by the miR-148a overexpressing cells contained more proteoglycans and collagen, in particular type II collagen. Proteoglycan and collagen release into the culture medium was inhibited, but total collagen production was increased. Overexpression of hsa-miR-148a inhibits hypertrophic differentiation and increases the production and deposition of type II collagen by OA chondrocytes, which is accompanied by an increased retention of proteoglycans. Hsa-miR-148a might be a potential disease-modifying compound in OA, as it promotes hyaline cartilage production.

Vonk LA ，Kragten AH ，Dhert WJ ，Saris DB ，Creemers LB ... -  《-》

Fibroblast Growth Factor Receptor 3 Inhibits Osteoarthritis Progression in the Knee Joints of Adult Mice.

Fibroblast growth factor (FGF) signaling is involved in articular cartilage homeostasis. This study was undertaken to investigate the role and mechanisms of FGF receptor 3 (FGFR-3) in the pathogenesis of osteoarthritis (OA) caused by surgery and aging in mice. FGFR-3 was conditionally deleted or activated in articular chondrocytes in adult mice subjected to surgical destabilization of the medial meniscus (DMM). A mouse model of human achondroplasia was also used to assess the role of FGFR-3 in age-associated spontaneous OA. Knee joint cartilage was histologically evaluated and scored using the Osteoarthritis Research Society International system. The expression of genes associated with articular cartilage maintenance was quantitatively evaluated in hip cartilage explants. The effect of inhibiting Indian hedgehog (IHH) signaling in Fgfr3-deficient explants was analyzed. Conditional Fgfr3 deletion in mice aggravated DMM-induced cartilage degeneration. Matrix metalloproteinase 13 and type X collagen levels were up-regulated, while type II collagen levels were down-regulated, in the articular cartilage of these mice. Conversely, FGFR-3 activation attenuated cartilage degeneration induced by DMM surgery and age. IHH signaling and runt-related transcription factor 2 levels in mouse articular chondrocytes were up-regulated in the absence of Fgfr3, while inhibition of IHH signaling suppressed the increases in the expression of Runx2, Mmp13, and other factors in Fgfr3-deficient mouse cartilage explants. Our findings indicate that FGFR-3 delays OA progression in mouse knee joints at least in part via down-regulation of IHH signaling in articular chondrocytes.

Tang J ，Su N ，Zhou S ，Xie Y ，Huang J ，Wen X ，Wang Z ，Wang Q ，Xu W ，Du X ，Chen H ，Chen L ... -  《-》