Abstract
Cartilage endplate (CEP) degeneration has been considered as one of important factors related to intervertebral disc degeneration (IVDD). Previous researches have showed that Rac1 played a pivotal role in chondrocyte differentiation. However, the effect of Rac1 during the process of CEP degeneration remains unclear. Herein, we explored the effect of Rac1 on CEP degeneration and elucidated the underlying molecular mechanism. We found expression of Rac1‐GTP increased in human‐degenerated CEP tissue and IL‐1β‐stimulated rat endplate chondrocytes (EPCs). Our study revealed that Rac1 inhibitor NSC23766 treatment promoted the expression of collagen II, aggrecan and Sox‐9, and decreased the expression of ADTAMTS5 and MMP13 in IL‐1β‐stimulated rat EPCs. Moreover, we also found that NSC23766 could suppress the activation of Wnt/β‐catenin pathway, suggesting that the beneficial effects of Rac1 inhibition in EPCs are mediated through the Wnt/β‐catenin signalling. Besides, puncture‐induced rats models showed that NSC23766 played a protective role on CEP and disc degeneration. Collectively, these findings demonstrated that Rac1 inhibition delayed the EPCs degeneration and its potential mechanism may be associated with Wnt/β‐catenin pathway regulation, which may help us better understand the association between Rac1 and CEP degeneration and provide a promising strategy for delaying the progression of IVDD.
Highlights
Intervertebral disc degeneration (IVDD) is considered as the crucial cause of low back pain, which influences approximately 80% of adults in different stages during their life-time.[1]
Wike et al have reported that Cartilage endplate (CEP) degeneration may be a possible contributor to the pathophysiology of disc degeneration, and its molecular mechanism involved the up-regulation of matrix-degrading enzymes and inflammatory cytokines.[5]
We found that the level of Rac[1] was elevated in human-degenerated CEP tissues and Rac[1] expression substantially increased by the proinflammatory factor IL-1β in a time-dependent manner comparing to the expression levels of Rac[1] in the untreated control group in rat endplate chondrocytes (EPCs)
Summary
Intervertebral disc degeneration (IVDD) is considered as the crucial cause of low back pain, which influences approximately 80% of adults in different stages during their life-time.[1]. Cartilage endplate (CEP) is an indispensable structure between the vertebral body and intervertebral disc, which was conducive. Wike et al have reported that CEP degeneration may be a possible contributor to the pathophysiology of disc degeneration, and its molecular mechanism involved the up-regulation of matrix-degrading enzymes and inflammatory cytokines.[5]. David et al have reported that Rac[1] signalling in chondrocytes stimulated by fibronectin fragment resulted in increased MMP13, which was involved in the cartilage matrix destruction.[13]. Wnt/β-catenin pathway has been demonstrated to play critical role in cartilage long-term function, which implicated in the regulation of cell proliferation, maintenance of phenotypic characteristics and chondrocyte differentiation.[15-17]. The intention of present study was to investigate the effect of Rac[1] in the degeneration of cartilaginous endplate and potential relationship with Wnt/β-catenin pathway through IL1β-induced endplate chondrocytes (EPCs) in vitro and rat annulus needle puncture models of IVDD in vivo.[22-24]. We suggested that Rac[1] inhibition could be a promising therapeutic strategy for CEP degeneration and even IVDD
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