The role of leptin on the organization and expression of cytoskeleton elements in nucleus pulposus cells

Zheng Li,Jinqian Liang,Jianxiong Shen,William Ka Kei Wu,Guixing Qiu,Jiaming Liu,Xin Yu

doi:10.1002/jor.22308

Abstract

Obesity is an important risk factor for intervertebral disc degeneration and leptin is a biomarker of obesity. However, the expression of leptin receptors has not been determined in disc tissue. It is not known whether leptin has a direct effect on the nucleus pulposus (NP) cells. To determine whether the NP tissues and cells express leptin receptors (OBRa and OBRb) and whether leptin affects the organization and the expression of major cytoskeletal elements in NP cells. Messenger RNA (mRNA) and protein levels of OBRa and OBRb were measured by real-time PCR and Western blot, respectively, in NP tissues and cells. Immunofluorescence and real-time PCR and Western blot were performed to investigate the effect of leptin on cytoskeleton reorganization and expression. Results show that mRNA and proteins of OBRa and OBRb were expressed in all NP tissues and cells, and that OBRb expression was correlated with patients' body weight. Increased expression of β-actin and reorganization of F-actin were evident in leptin-stimulated NP cells. Leptin also induced vimentin expression but had no effect on β-tubulin in NP cells. These findings provide novel evidence supporting the possible involvement of leptin in the pathogenesis of intervertebral disc degeneration. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 847–857, 2013

Highlights

Low back pain is a common disorder, which has a lifetime prevalence of about 70%.1 Disc degeneration of the lumbar spine is considered to be one of the underlying factors of low back pain
Expression of Leptin Receptors in nucleus pulposus (NP) Tissues and Cells was Correlated with body mass index (BMI) The Messenger RNA (mRNA) and protein of OBRa and OBRb were expressed in all human NP tissues and NP cells (Figs. 1 and 6)
Accumulating evidence from epidemiological studies indicates that high body mass index (BMI) increases the risk of lumbar disc degeneration (LDD).[18]

Summary

Introduction

Low back pain is a common disorder, which has a lifetime prevalence of about 70%.1 Disc degeneration of the lumbar spine is considered to be one of the underlying factors of low back pain. The almost universal distribution of OBRa and OBRb reflects the pleiotropic biological effects of leptin in non-adipose tissues, providing evidence for the extreme functional diversity of leptin.[8] Previous studies have demonstrated the human intervertebral disc cells can secret detectable levels of leptin.[9] Zhao et al.[10] have shown that disc cells express leptin functional receptor whose expression is correlated with the age of the patients. The contribution of body weight to the regulation of the leptin-receptor expression in human intervertebral disc remains elusive. The behavior of mature intervertebral disc cells depends on the organization and composition of their cytoskeleton.[12] Our recent work observed that leptin may be involved in the pathophysiology of osteoarthritis via induction of cytoskeletal reorganization in chondrocytes.[13]

Objectives

Methods

Results

Conclusion