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- Title
Leptin-mediated cytoskeletal remodeling in chondrocytes occurs via the RhoA/ROCK pathway.
- Authors
Jinqian Liang; Juefei Feng; William Ka Kei Wu; Jun Xiao; Zhihong Wu; Dong Han; Yong Zhu; Guixing Qiu
- Abstract
Leptin affects a number of cell signaling pathways, at present, the mechanism(s) by which leptin affects the cartilage cells in OA patient is not well understood. The current study seeks to elucidate whether leptin induces cytoskeletal remodeling in chondrocytes and the possible involvement of the RhoA/ROCK pathway and its downstream mediators in this process. Fluorescent resonance energy transfer (FRET) and western analysis were used to determine the activations of the key proteins in the RhoA/LIMK1/Cofilin pathway. Accompanying cytoskeletal remodeling was elucidated. Upon leptin stimulation, a substantial increase of RhoA activity localized at one end of the cell was observed from 2 to 30 min post-stimulation. The results of Western blot showed leptin significantly increased LIMK1 and cofilin-2 phosphorylation in a time-dependent manner with maximal stimulation attained 60 min and 24 h post-stimulation, respectively. Chondrocytes stimulated with leptin exhibited an epithelioid morphology with increased cellular spreading. F-actin in leptin-stimulated chondrocytes also showed more intense cytoplasmic staining with occasional localization along filamentous structures. The results indicate that leptin activates the RhoA/ROCK/LIMK/cofilin pathway, which results in cytoskeletal reorganization in chondrocytes. These findings provide novel evidence supporting the possible involvement of leptin and the RhoA pathway in the pathogenesis of OA. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:369-374, 2011
- Publication
Journal of Orthopaedic Research, 2011, Vol 29, Issue 3, p369
- ISSN
0736-0266
- Publication type
Article
- DOI
10.1002/jor.21257