Biochemical changes in extra-cellular matrix in equine degenerative suspensory ligament desmitis
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Degenerative suspensory ligament desmitis (DSLD) is a debilitating disorder thought to be limited to suspensory ligaments of Peruvian Pasos, Peruvian Paso crosses, and other horse breeds. It frequently leads to persistent, incurable lameness. The pathogenesis remains unclear, though the disease appears to run in families. Presently, there are no reliable methods of diagnosing DSLD in asymptomatic horses. The goal of this study was to characterize and define the disorder in terms of tissue involvement at the macroscopic and microscopic levels and to identify mechanism of this disease with special attention given to small leucine rich proteoglycans (SLRPs), decorin and fibromodulin. We examined tissues and organs from DSLD affected and control horses. Histopathological examination revealed excessive accumulation of proteoglycans in the following tissues: suspensory ligaments, superficial and deep digital flexor tendons, patellar and nuchal ligaments, cardiovascular system, and sclerae. Electron microscopy demonstrated changes in diameters of collagen fibrils in tendons, and in smooth muscle cells of the media of the aorta. In biochemical analysis, the proteoglycan overexpressed in affected tendon extracts was identified as decorin. Upon purification from affected tendons, we have demonstrated presence of a higher molecular weight (~140kDa) decorin. The content of chondrotin-6-sulfate and the glucuronic acid of dermatan sulfate of this abnormal decorin were increased. ELISA showed that this decorin exhibited lower affinity to TGF²1 than normal decorin. An increase in higher molecular fibromodulin in affected tendons was also observed. This study demonstrates for the first time that DSLD is a systemic disorder characterized by accumulation of modified proteoglycans in tissues and organs with a significant connective tissue component. We, therefore, propose that equine systemic proteoglycan accumulation or ESPA rather than DSLD is a more appropriate name for this condition. Our biochemical results indicate that decorin and fibromodulin from ESPA affected tendons undergo changes in glycosylation of their glycosaminoglycans chains. In addition decorin purified from ESPA-affected tendons had low affinity to TGF²1, which might lead to overxpression of TGF²1 in tissues. These changes in expression of TGF²1 by abnormal proteoglycan might contribute to the development of clinical picture observed in horses suffering from ESPA.