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Leptin induces oncostatin M production in osteoblasts by downregulating miR-93 through the Akt signaling pathway.


ABSTRACT: 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.

SUBMITTER: Yang WH 

PROVIDER: S-EPMC4200751 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Leptin induces oncostatin M production in osteoblasts by downregulating miR-93 through the Akt signaling pathway.

Yang Wei-Hung WH   Tsai Chun-Hao CH   Fong Yi-Chin YC   Huang Yuan-Li YL   Wang Shoou-Jyi SJ   Chang Yung-Sen YS   Tang Chih-Hsin CH  

International journal of molecular sciences 20140905 9


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-d  ...[more]

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