Abstract
Progressive matrix metalloproteinase (MMP)-induced degradation of the extracellular matrix (ECM) of the articular cartilage is one of the major pathogenic osteoarthritis (OA) events. Several single nucleotide polymorphisms (SNPs) in genes encoding MMPs have been identified as affecting MMP expression, production, and enzymatic activity. This study systematically reviews the literature regarding the association between the SNPs of genes encoding MMPs and the risk of knee OA. An electronic search in the PubMed and Web of Science databases from conception to January 2021 was performed addressing studies relating MMPs genetic polymorphisms with the risk of knee OA. We included case-control studies that used validated genotyping methods to detect the SNPs’ association in MMP genes with primary knee OA risk. Ten studies were finally included in this systematic review, evaluating different SNPs in six MMP genes in terms of knee OA pathogenesis: MMP-1 (3 SNPs), MMP-2 (1 SNP), MMP-3 (9 SNPs), MMP-8 (10 SNPs), MMP-9 (6 SNPs), and MMP-13 (1 SNP). Among them, nine SNPs of four MMP genes have been associated with knee OA: (a) MMP-1 -1607 1G/2G (Turkish, Chinese), (b) MMP-3 rs650108, rs650108, rs520540, rs602128, rs679620 (Chinese), (c) MMP-8 rs1940475 and rs376520 (Finnish), and (d) MMP-13 77A/ (rs2252070) (Chinese). The present review summarizes all known SNPs of MMP genes related to a higher risk of knee OA. There are at least nine SNPs in four MMP genes associated with knee OA. No solid correlation between MMP genotype and knee OA phenotype exists. More high-quality studies and modern genetic testing methods are needed to fully elucidate the role of polymorphisms of MMP genes in knee OA pathogenesis.
Highlights
BackgroundOsteoarthritis (OA) is one of the leading causes of pain and disability worldwide
The progressive degradation of the extracellular matrix (ECM) of the articular cartilage is one of the major pathogenetic events leading to exposure and wear of the subchondral bone, osteophytes formation, and eventually to OA
matrix metalloproteinase (MMP) are involved in a plethora of complicated biological actions in both standard and pathological conditions
Summary
Osteoarthritis (OA) is one of the leading causes of pain and disability worldwide. It is a degenerative disease that mostly affects the articular cartilage, consisting mainly of chondrocytes and extracellular matrix (ECM). The integrity of articular cartilage is maintained by the equilibrium between anabolic and catabolic processes. Any alterations in this balance may contribute to the destructive process within the joint [1]. The progressive degradation of the ECM of the articular cartilage is one of the major pathogenetic events leading to exposure and wear of the subchondral bone, osteophytes formation, and eventually to OA. The etiology of OA is not fully elucidated and may involve complex interactions between genetic and environmental factors [2]
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