Leptin Induces Oncostatin M Production in Osteoblasts by Downregulating miR-93 through the Akt Signaling Pathway

International Journal of Molecular Sciences

Wei-Hung Yang⁵  Chun-Hao Tsai¹  Yi-Chin Fong³  Yuan-Li Huang²  Shoou-Jyi Wang⁴  Yung-Sen Chang⁵ 

[1] Department of Medicine and Graduate Institute of Clinical Medical Science, China Medical University, Taichung 404, Taiwan; E-Mail:;Department of Biotechnology, College of Health Science, Asia University, Taichung 500, Taiwan; E-Mail:;School of Chinese Medicine, College of Chinese Medicine,China Medical University, Taichung 404, Taiwan; E-Mail:;Department of Orthopedic Surgery, Chang-Hua Hospital, Department of Health Executive Yuan, Changhua Country 500, Taiwan; E-Mail:;Department of Orthopedic Surgery, Taichung Hospital, Department of Health Executive Yuan, Taichung 403, Taiwan; E-Mails:

关键词: leptin;    oncostatin M;    OBRl;    arthritis;    miR-93;   

DOI  :  10.3390/ijms150915778

来源: mdpi

【 摘 要 】

Inflammatory response and articular destruction are common symptoms of osteoarthritis (OA) and rheumatoid arthritis (RA). Leptin, an adipocyte-secreted hormone that centrally regulates weight control, may exert proinflammatory effects in the joint, depending on the immune response. Yet, the mechanism of leptin interacting with the arthritic inflammatory response is unclear. This study finds that leptin increased expression of oncostatin M (OSM) in human osteoblasts in a concentration- and time-dependent manner. In addition, OBRl, but not OBRs receptor antisense oligonucleotide, abolished the leptin-mediated increase of OSM expression. On the other hand, leptin inhibited miR-93 expression; an miR-93 mimic reversed leptin-increased OSM expression. Stimulation of osteoblasts with leptin promoted Akt phosphorylation, while pretreatment of cells with Akt inhibitor or siRNA reversed leptin-inhibited miR-93 expression. Our results showed that leptin heightened OSM expression by downregulating miR-93 through the Akt signaling pathway in osteoblasts, suggesting leptin as a novel target in arthritis treatment.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.