Down-regulation of microRNA-216b inhibits IL-1β-induced chondrocyte injury by up-regulation of Smad3.

Osteoarthritis (OA) is the most common type of joint disease, leading to a major cause of pain and disability. OA is characterized by the continuous degradation of articular cartilage, mainly resulting in an imbalance between synthesis and degradation of articular chondrocyte extracellular matrix (ECM). Aberrant miR-216b expression has been found in multiple cancers. However, the level of miR-216b in OA cartilage and its role in progression of this disease are still unknown. In the present study, the functional roles of miR-216b and its expression in OA tissues and interleukin-1β (IL-1β)-induced chondrocytes were examined. We found that the level of miR-216b was significantly higher and Smad3 expression was obviously lower in OA cartilage and IL-1β-induced chondrocytes than in normal tissues and cells. Furthermore, a bioinformatics analysis and luciferase reporter assay identified Smad3 as a direct target gene of miR-216b, and Smad3 expression was reduced by miR-216b overexpression at both the mRNA and protein levels. A functional analysis demonstrated that miR-216b down-regulation obviously alleviated the IL-1β-induced inhibition in cell proliferation, type II collagen, and aggrecan down-regulation and matrix metalloproteinase-13 (MMP-13) up-regulation, while miR-216b overexpression had the opposite effects. Knockdown of Smad3 by siRNA reversed the effects of the miR-216b inhibitor on cell proliferation, the expressions of type II collagen, aggrecan, and MMP-13. Our results suggested that miR-216b contributes to progression of OA by directly targeting Smad3, providing a potential therapeutic target for treatment of OA.

He J ，Zhang J ，Wang D 《-》

Mechanical and IL-1β Responsive miR-365 Contributes to Osteoarthritis Development by Targeting Histone Deacetylase 4.

Yang X ，Guan Y ，Tian S ，Wang Y ，Sun K ，Chen Q ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Downregulation of microRNA-448 inhibits IL-1β-induced cartilage degradation in human chondrocytes via upregulation of matrilin-3.

Yang H ，Wu D ，Li H ，Chen N ，Shang Y ... -  《-》

Downregulation of miR-221-3p contributes to IL-1β-induced cartilage degradation by directly targeting the SDF1/CXCR4 signaling pathway.

Zheng X ，Zhao FC ，Pang Y ，Li DY ，Yao SC ，Sun SS ，Guo KJ ... -  《-》

MicroRNA-23a-3p promotes the development of osteoarthritis by directly targeting SMAD3 in chondrocytes.

Osteoarthritis (OA) is a common chronic degenerative joint disease. Progressive destruction of the integrity of articular cartilage is an important pathological feature, but treatment options that reverse this damage have not been developed. According to recent studies, microRNAs have important regulatory roles in the initiation and progression of OA. In the current study, the biological effects of miR-23a-3p and its expression in OA tissues were examined. We found that miR-23a-3p expression was obviously higher and SMAD3 expression was significantly lower in OA cartilage than in normal tissues. The hypomethylation status of CpG islands in the promoter region of miR-23a-3p was confirmed by methylation-specific polymerase chain reaction in OA cartilage tissues. Furthermore, a bioinformatics analysis and luciferase reporter assay identified SMAD3 as a target gene of miR-23a-3p and SMAD3 expression at both the protein and mRNA levels was inhibited by miR-23a-3p. A functional analysis demonstrated that miR-23a-3p overexpression suppresses type II collagen and aggrecan expression, while miR-23a-3p inhibition had the opposite effects. Small interfering RNA-mediated knockdown of SMAD3 reversed the effects of the miR-23a-3p inhibitor on the expression of type II collagen and aggrecan. Our results suggested that miR-23a-3p contributes to OA progression by directly targeting SMAD3, providing a potential therapeutic target for OA treatment.

Kang L ，Yang C ，Song Y ，Liu W ，Wang K ，Li S ，Zhang Y ... -  《-》