Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk 570-749, Republic of Korea.
Biochem Biophys Res Commun. 2013 Feb 8;431(2):210-4. doi: 10.1016/j.bbrc.2012.12.133. Epub 2013 Jan 9.
MicroRNAs are endogenous gene regulators that have been implicated in various developmental and pathological processes. However, the precise identities and functions of the miRNAs involved in cartilage development are not yet well understood. Here, we report that miR-181b regulates chondrocyte differentiation and maintains cartilage integrity, and is thus a potent therapeutic target. MiR-181b was significantly down-regulated during chondrogenic differentiation of TGF-β3-stimulated limb mesenchymal cells, but it was significantly up-regulated in osteoarthritic chondrocytes isolated from the cartilage of osteoarthritis patients. The use of a mimic or an inhibitor to alter miR-181b levels in chondroblasts and articular chondrocytes showed that attenuation of miR-181b reduced MMP-13 expression while inducing type II collagen expression. Furthermore, over-expression of anti-miR-181b significantly reduced the cartilage destruction caused by DMM surgery in mice. In sum, our data suggest that miR-181b is a negative regulator of cartilage development, and that inhibition of miR-181b could be an effective therapeutic strategy for cartilage-related disease.
微小 RNA 是内源性基因调控因子，参与多种发育和病理过程。然而，参与软骨发育的 miRNA 的确切身份和功能尚不清楚。在这里，我们报告 miR-181b 调节软骨细胞分化并维持软骨完整性，因此是一个有效的治疗靶点。在 TGF-β3 刺激的肢间充质细胞的软骨分化过程中，miR-181b 显著下调，但在从骨关节炎患者软骨中分离的骨关节炎软骨细胞中显著上调。使用模拟物或抑制剂改变软骨细胞和成软骨细胞中的 miR-181b 水平表明，miR-181b 的衰减降低了 MMP-13 的表达，同时诱导了 II 型胶原的表达。此外，过表达抗 miR-181b 显著减少了 DMM 手术引起的小鼠软骨破坏。总之，我们的数据表明 miR-181b 是软骨发育的负调节剂，抑制 miR-181b 可能是一种治疗与软骨相关疾病的有效策略。
