Matrix metalloproteases: a role in overuse tendinopathies
- Department of Trauma and Orthopaedic Surgery, Keele University School of Medicine, Stoke on Trent, Staffordshire, UK
- Correspondence to: Professor Maffulli Department of Trauma and Orthopaedic Surgery, Keele University School of Medicine, Thornburrow Drive, Hartshill, Stoke on Trent ST4 7QB, Staffordshire, UK; osa14keele.ac.uk
The balance between matrix metalloproteases and their inhibitors is important in maintaining healthy tendons
Tendinopathy is a broad term used to describe disorders in and around tendons, with absence of inflammatory cells and a poor healing response, demonstrated by collagen fibrils separated from each other lengthwise and disrupted in cross section. Tendinitis, tendinosis, and paratenonitis are all examples of tendinopathy.1
MATRIX METALLOPROTEASES (MMPS) AND TISSUE INHIBITORS OF METALLOPROTEASES (TIMPS)
MMPs, a family of zinc and calcium dependent endopeptidases active at a neutral pH, are involved in the remodelling of extracellular matrix (ECM) through their broad proteolytic capability.2 Degradation of collagen in tendon ECM is initiated by MMPs.3 Twenty three human MMPs have been identified,2 with a wide range of extracellular substrates (table 1).4,5 MMPs can be subdivided into four main groups: collagenases, which cleave native collagen types I, II, and III; gelatinases, which cleave denatured collagens and type IV collagen; stromelysins, which degrade proteoglycans, fibronectin, casein, collagen types III, IV, and V; membrane-type MMPs.5
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The main components of the matrix metalloprotease (MMP) family
The activity of MMPs is inhibited reversibly by TIMPs in a non-covalent fashion in a 1:1 stoichiometry.5 There are four types of TIMP: TIMP1, TIMP2, TIMP3, and TIMP4.5 The balance between the activities of MMPs and TIMPs regulates tendon remodelling, and an imbalance produces collagen disturbances in tendons.6
ROLE OF MMPS AND TIMPS IN TENDINOPATHY
MMP3 may play a major role in regulation of tendon ECM degradation and tissue remodelling. An increased expression of MMP3 may be necessary for appropriate tissue remodelling and prevention of tendinopathic changes.7 The timing of MMP3 production is probably also …
