Leptin Activates RhoA/ROCK Pathway to Induce Cytoskeleton Remodeling in Nucleus Pulposus Cells

International Journal of Molecular Sciences

Zheng Li¹  Jinqian Liang¹  William Ka Kei Wu²  Xin Yu¹  Jun Yu²  Xisheng Weng¹ 

[1] Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China; E-Mails:;Institute of Digestive Disease and State Key Laboratory of Digestive Diseases, Department of Medicine and Therapeutics and LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China; E-Mails:

关键词: disc degeneration;    fluorescent resonance energy transfer (FRET);    cytoskeleton;    leptin;    F-actin;   

DOI  :  10.3390/ijms15011176

来源: mdpi

【 摘 要 】

Hyperleptinemia is implicated in obesity-associated lumbar disc degeneration. Nevertheless, the effect of leptin on the intracellular signaling of nucleus pulposus cells is not clear. The current study sought to delineate the possible involvement of the RhoA/ROCK pathway in leptin-mediated cytoskeleton reorganization in nucleus pulposus cells. Nucleus pulposus cells isolated from scoliosis patients were treated with 10 ng/mL of leptin. Fluorescent resonance energy transfer analysis was used to determine the activation of RhoA signaling in nucleus pulposus cells. The protein expression of LIMK1 and cofilin-2 were analyzed by western blot analysis. F-actin cytoskeletal reorganization was assessed by rhodamine-conjugated phalloidin immunoprecipitation. Leptin induced F-actin reorganization and stress fiber formation in nucleus pulposus cells, accompanied by localized RhoA activation and phosphorylation of LIMK1 and cofilin. The RhoA inhibitor C3 exoenzyme or the ROCK inhibitor Y-27632 potently attenuated the effects of leptin on F-actin reorganization and stress fiber formation. Both inhibitors also prevented leptin-induced phosphorylation of LIMK1 and cofilin-2. Our study demonstrated that leptin activated the RhoA/ROCK/LIMK/cofilin-2 cascade to induce cytoskeleton reorganization in nucleus pulposus cells. These findings may provide novel insights into the pathogenic mechanism of obesity-associated lumbar disc degeneration.

【 授权许可】

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© 2014 by the authors; licensee MDPI, Basel, Switzerland