School of Medicine
Osteoarthritis (OA) is characterized by the progressive destruction of articular cartilage, which is involved in the imbalance between extracellular matrix (ECM) synthesis and degradation. MicroRNA-140-5p (miR-140) is specifically expressed in cartilage and plays an important role in OA-induced matrix degradation. The aim of this study was to investigate (1) whether intra-articular injection of melatonin could ameliorate surgically induced OA in mice and (2) whether melatonin could regulate matrix-degrading enzymes at the posttranscriptional level by targeting miR-140. In an in vitro OA environment induced by interleukin-1 beta (IL-1β), melatonin treatment improved cell proliferation of human chondrocytes, promoted the expression of cartilage ECM proteins (e.g., type II collagen and aggrecan), and inhibited the levels of IL-1β-induced proteinases, such as matrix metalloproteinase 9 (MMP9), MMP13, ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4), and ADAMTS5. Both the microarray and polymerase chain reaction (PCR) experiments revealed that miR-140 was a melatonin-responsive microRNA and melatonin upregulated miR-140 expression, which was suppressed by IL-1β stimulation. In vivo experiments demonstrated that intra-articular injection of melatonin prevented disruptions of cartilage matrix homeostasis and successfully alleviated the progression of surgery-induced OA in mice. Transfection of miR-140 antagomir completely counteracted the antiarthritic effects of melatonin by promoting matrix destruction. Our findings demonstrate that melatonin protects the articular cartilage from OA-induced degradation by targeting miR-140, and intra-articular administration of melatonin may benefit patients suffering from OA.
Digital Commons Citation
Zhang, Yijian; Lin, Jun; Zhou, Xinfeng; Chen, Xi; Chen, Angela Carley; Pi, Bin; Pan, Guoquing; Pei, Ming; Yang, Huilin; Liu, Tao; and He, Fan, "Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation via Targeting MicroRNA-140" (2019). Faculty & Staff Scholarship. 1357.
Zhang, Y., Lin, J., Zhou, X., Chen, X., Chen, A. C., Pi, B., Pan, G., Pei, M., Yang, H., Liu, T., & He, F. (2019). Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation via Targeting MicroRNA-140. Oxidative Medicine and Cellular Longevity, 2019, 1–16. https://doi.org/10.1155/2019/9705929