title: Leptin induces osteocalcin expression in ATDC5 cells through activation of the MAPK-ERK1/2 signaling pathway.
abstract: Both leptin and osteocalcin have been found to affect growth-plate cartilage development through regulation of the physiologic processes of endochondral bone formation. Leptin mediates bone development and osteocalcin secreted in the late stage of osteoblast differentiation. The relationship between leptin and osteocalcin expression in the chondrogenic cells line is still not clear. Thus, the aim of this study was to explore the effect of leptin on the expression of osteocalcin in chondrocytes. We used clonal mouse chondrogenic ATDC5 cells to investigate the relationship between leptin and osteocalcin. We found that both leptin and osteocalcin expression were dynamically expressed during ATDC5 cell differentiation from 4 to 21 days. We also found that leptin significantly upregulated osteocalcin mRNA and protein levels 24 h after leptin stimulation. However, different concentrations and exposure times of osteocalcin did not affect the levels of leptin protein. Furthermore, we confirmed that leptin augmented the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in a time-dependent manner but not p38 or AKT. Inhibition of pERK1/2 expression by a specific ERK1/2 inhibitor U0126 and a special small interfering RNA attenuated levels of leptin-induced osteocalcin expression, indicating that ERK1/2 mediates, in part, the effects of leptin on osteocalcin. Taken together, our results suggest that leptin regulates the expression of osteocalcin in growth plate chondrocytes via the ERK1/2 signaling pathway, while there is no effect on the phosphorylation of either p38 or AKT.
authors: Department of Spine Surgery, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, 200120, China.
authors: Yingchao
authors: Y
authors: Han
authors: Department of Orthopedics, Shanghai Zhabei District Central hospital, Zhonghuaxin Road Zhabei District, Shanghai, 200070, China.
authors: Guanghui
authors: G
authors: Xu
authors: Department of Spine Surgery, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, 200120, China.
authors: Jingjie
authors: J
authors: Zhang
authors: Department of Spine Surgery, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, 200120, China.
authors: Meijun
authors: M
authors: Yan
authors: Department of Spine Surgery, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, 200120, China.
authors: Xinhua
authors: X
authors: Li
authors: Department of Spine Surgery, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, 200120, China.
authors: Bin
authors: B
authors: Ma
authors: Department of Spine Surgery, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, 200120, China.
authors: Lili
authors: L
authors: Jun
authors: Department of Spine Surgery, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, 200120, China.
authors: Shan-Jin
authors: SJ
authors: Wang
authors: Department of Spine Surgery, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, 200120, China.
authors: Jun
authors: J
authors: Tan
mesh_terms: D000818:Animals; D002070:Butadienes / Q000737:chemistry; D002452:Cell Count; D002454:Cell Differentiation; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology*; D020219:Chondrogenesis / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009570:Nitriles / Q000737:chemistry; D010006:Osteoblasts / Q000166:cytology; D015675:Osteocalcin / Q000097:blood / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D002070:Butadienes; D020738:Leptin; D009570:Nitriles; D034741:RNA, Small Interfering; C113580:U 0126; D015675:Osteocalcin; D048049:Extracellular Signal-Regulated MAP Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases
keywords: ATDC5; chondrocyte; growth plate; leptin; osteocalcin