In a series of articles, researchers in the Tendon Biology group at the RVC have established the importance of inflammatory mediators in acute tendon disease and the reduced ability to resolve inflammation in chronic disease and in older individuals. In their most recent study published in the Journal of Biological Chemistry, Dr Stephanie Dakin from the group and collaborators at the University of Lund, Sweden, investigated the subtle protein cleavages induced by inflammation in normal and injured equine flexor tendons using a proteomics approach.
The study showed that tendon injury resulted in extensive and irreversible remodelling of the extracellular matrix (ECM). When the researchers focused on cartilage oligomeric matrix protein (COMP), an abundant protein in tendons, cleaved fragments of this protein were found to correlate with early and late stage injury. This work shows that not only do inflammatory mediators lead to specific cleavage of ECM proteins but also suggests that a hierarchical and sequential activity of metalloproteinases exist during different disease phases.
This work enhances understanding of the mechanisms involved in inflammation-mediated tendon degeneration. Furthermore, the identification of novel neo-terminal COMP fragments provides the foundation to develop biomarkers for tendinopathy, such that subclinical and acute tendon injuries in the horse may be identified and treated promptly.
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Dakin SG, Smith RK, Heinegard D, Onnerfjord P, Khabut A, Dudhia J. "Proteomic analysis of tendon extracellular matrix reveals disease stage-specific fragmentation and differential cleavage of COMP." J Biol Chem. 2014 Jan. DOI: 10.1074/jbc.M113.511972.