Abstract
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.
Highlights
Obesity, defined as body mass index (BMI) exceeding 30 kg/m2, is a serious public health issue.Globally, more than one billion adults and children are overweight [1]
Leptin Activated the RhoA Signaling in nucleus pulposus (NP) Cells
We determined if leptin could affect RhoA signaling in NP cells
Summary
Obesity, defined as body mass index (BMI) exceeding 30 kg/m2, is a serious public health issue.Globally, more than one billion adults and children are overweight [1]. Obesity is associated with increased risks for various morbidities, including cardiovascular diseases, diabetes, osteoarthritis, and spinal diseases [2]. To this end, obesity is an established risk factor for intervertebral disc degeneration, which is considered to be one of the major etiological factors of low back pain [3]. Aside from mechanical stress, increased circulating levels of obesity-associated hormones, such as sex steroids, insulin, insulin-like growth factor 1, and leptin, are potential pathogenic mediators in obesity-associated lumbar disc degeneration (LDD) [5]. In humans, serum leptin levels correlate closely with body mass and may increase from 1–3 ng/mL in non-obese subjects to as high as 100 ng/mL in obese individuals [8]
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