Role of metalloproteinases and their inhibitors in intervertebral disc degeneration:research progress

Intervertebral disc degeneration(IVDD)is characterized by the excessive degradation of extracellular matrix(ECM),which underlies many spine-related disorders.Matrix metalloproteinases(MMPs)and a disintegrin metalloproteinases with thrombospondin motifs(ADAMTSs)are believed to be the major proteolytic enzymes responsible for ECM degradation.This review summarizes the current literatures on gene expression and regulation of MMPs,ADAMTSs,and tissue inhibitors of metalloproteinases(TIMPs)in IVDD.Reports have showen that specific MMPs(MMP-1,-2,-3,-7,-8,-10,and-13)and ADAMTS(ADAMTS-1,-4,and-15)are upregulated in human degenerated intervertebral discs.Tissue inhibitor of metalloproteinase-3is downregulated and TIMP-1 is upregulated in human degenerated intervertebral discs relative to nondegenerated intervertebral discs.Regulation of the MMP and ADAMTS expression is affected by many factors including mechanical,inflammatory,oxidative stress,and so on.Genetic predisposition also plays an important role in expression of MMP-1,-2,-3,and-9.Upregulation of MMP and ADAMTS expression is implicated in ECM destruction,which can lead to the development of IVDD.Future IVDD therapeutics may target specific MMPs and ADAMTSs which is essential in the pathological proteolysis of ECM.