elastin and Osteolysis

Calcinosis cutis, defined as sub-epidermal deposition of calcium salts, is a major clinical problem in patients with SSc, affecting 20-40% of patients. A number of recognized factors associated with calcinosis have been identified, including disease duration, digital ischaemia and acro-osteolysis. Yet, to date, the pathogenesis of SSc-related calcinosis remains unknown, and currently there is no effective disease-modifying pharmacotherapy. Following onset of SSc, there are marked changes in the extracellular matrix (ECM) of the skin, notably a breakdown in the microfibrillar network and accumulation of type I collagen. Our hypothesis is that these pathological changes reflect a changing cellular phenotype and result in a primed microenvironment for soft tissue calcification, with SSc fibroblasts adopting a pro-osteogenic profile, and specific driving forces promoting tissue mineralization. Considering the role of the ECM in disease progression may help elucidate the mechanism(s) behind SSc-related calcinosis and inform the development of future therapeutic interventions.

Topics: Calcinosis; Cell Differentiation; Cell Hypoxia; Cellular Microenvironment; Collagen Type I; Disease Progression; Elastin; Extracellular Matrix; Fibrillin-1; Fibroblasts; Glucose Transporter Type 1; Humans; Mesenchymal Stem Cells; Myofibroblasts; Osteoblasts; Osteogenesis; Osteolysis; Phenotype; Phosphates; Scleroderma, Systemic; Skin; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A