Role of p38-MAPK pathway in the effects of high-magnitude compression on nucleus pulposus cell senescence in a disc perfusion culture.

Lianglong Pang,Qiang Zhou,Lei Song,Yuan Xu,Pei Li,Ruijie Zhang

doi:10.1042/bsr20170718

Abstract

Nucleus pulposus (NP) cell senescence is a typical pathological feature within the degenerative intervertebral disc. As a potential inducing and aggregating factor of disc degeneration, mechanical overloading affects disc biology in multiple ways. The present study was to investigate the NP cell senescence-associated phenotype under intermittent high compression in an ex vivo disc bioreactor culture, and the role of the p38–MAPK pathway in this regulatory process. Porcine discs were cultured in culture chambers of a self-developed mechanically active bioreactor and subjected to different magnitudes of dynamic compression (low-magnitude and high-magnitude: 0.1 and 1.3 MPa at a frequency of 1.0 Hz for 2 h per day respectively) for 7 days. Non-compressed discs were used as controls. The inhibitor SB203580 was used to study the role of the p38–MAPK pathway in this process. Results showed that intermittent high-magnitude compression clearly induced senescence-associated changes in NP cells, such as increasing β-galactosidase-positive NP cells, decreasing PCNA-positive NP cells, promoting the formation of senescence-associated heterochromatic foci (SAHF), up-regulating the expression of senescence markers (p16 and p53), and attenuating matrix production. However, inhibition of the p38–MAPK pathway partly attenuated the effects of intermittent high-magnitude (1.3 MPa) compression on those described NP cell senescence-associated parameters. In conclusion, intermittent high-magnitude compression can induce NP cell senescence-associated changes in an ex vivo disc bioreactor culture, and the p38–MAPK pathway is involved in this process.

Highlights

Intervertebral disc degeneration is regarded as a major cause of lower back pain [1]
To verify whether the p38–MAPK pathway participated in the described effects of intermittent high-magnitude compression on nucleus pulposus (NP) cell senescence, the inhibitor SB203580 effectively inhibited activation of the p38–MAPK pathway both in the control group and the 1.3 MPa+SB group (Figure 2B)
We studied the effect of mechanical compression on NP cell senescence in an ex vivo disc bioreactor culture

Summary

Introduction

Intervertebral disc degeneration is regarded as a major cause of lower back pain [1]. This physical disability products substantial economic burdens on social health care systems and great inconvenience to the daily activity of patients [2]. Senescent cells can remain viable for a long time, their morphology, and biological function largely differ from non-senescent cells. This transition into the senescent phenotype directly causes cell c 2017 The Author(s).

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Results

Conclusion