title: Leptin induces terminal differentiation of rat annulus fibrosus cells via activation of MAPK signaling.
abstract: Both leptin and its receptor are expressed in rat annulus fibrosus (AF) cells. However, little is known about their role and mechanism during disc degeneration. The mitogen activating protein kinase (MAPK) pathway which mediates leptin-induced terminal differentiation of rat AF cells was analyzed using PCR, Western-blot and immunocytochemistry. It was found that leptin-induced AF cells terminal differentiation, which may be attributed to upregulated p38 and ERK1/2 phosphorylation, however, JNK phosphorylation was not observed. Specific inhibitors of p38 or ERK1/2, but not JNK, could inhibit the stimulative activity of leptin on collagen X and MMP-13 protein levels. This study, for the first time, shows that the MAPK pathway, especially p38 and ERK1/2 signaling, plays a distinct role in leptin-induced AF cells terminal differentiation.
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhao
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Youzhuanu
authors.initials: Y
authors.lastname: Xie
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D007124:Immunoenzyme Techniques; D007403:Intervertebral Disc / Q000166:cytology* / Q000187:drug effects*; D020738:Leptin / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D020738:Leptin; D012333:RNA, Messenger; D020928:Mitogen-Activated Protein Kinases
keywords: MAPK; annulus fibrosus cells; leptin; terminal differentiation