TY - JOUR
T1 - Systemic sclerosis skin is a 'primed' microenvironment for soft tissue calcification - a hypothesis
AU - Burgess, Kyle A
AU - Herrick, Ariane L
AU - Watson, Rachel E B
N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: [email protected].
PY - 2021/2/15
Y1 - 2021/2/15
N2 - Calcinosis cutis, defined as sub-epidermal deposition of calcium salts, is a major clinical problem in patients with systemic sclerosis (SSc), affecting 20-40% of patients. A number of recognised associates of 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 mineralisation. 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.
AB - Calcinosis cutis, defined as sub-epidermal deposition of calcium salts, is a major clinical problem in patients with systemic sclerosis (SSc), affecting 20-40% of patients. A number of recognised associates of 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 mineralisation. 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.
U2 - 10.1093/rheumatology/keab156
DO - 10.1093/rheumatology/keab156
M3 - Article
C2 - 33585894
SN - 1462-0324
VL - 60
SP - 2517
EP - 2527
JO - Rheumatology (Oxford, England)
JF - Rheumatology (Oxford, England)
IS - 6
ER -
