Carrie Richardson1,2, Anna Plaas3, John Varga4. 1. Rush University Medical Center, Chicago, IL, USA. carrie_richardson@rush.edu. 2. , Chicago, USA. carrie_richardson@rush.edu. 3. Rush University Medical Center, Chicago, IL, USA. 4. Northwestern University, Chicago, IL, USA.
Abstract
PURPOSE OF REVIEW: Calcinosis is a common complication of systemic sclerosis with no known effective pharmacologic therapy. We reviewed the literature regarding systemic sclerosis-related calcinosis as well as other disorders of biomineralization in order to identify targets of future study for calcinosis. RECENT FINDINGS: Patients with systemic sclerosis-related calcinosis demonstrate systemic abnormalities in mineralization pathways, including decreased levels of the mineralization inhibitor inorganic pyrophosphate. Insights from other mineralization disorders suggest that local and systemic phosphate metabolism pathways involving the ABCC6, ENPP1, and NT5E genes play a critical role in regulation of ectopic calcification. Knockout models of these genes may lead to an appropriate murine model for study of calcinosis. Poly(ADP-ribose) polymerase (PARP) enzymes may also play a critical role in hydroxyapatite nucleation and warrant future study in systemic sclerosis. Study of local and systemic mineralization pathways, particularly phosphate metabolism pathways and PARP enzymes, should provide greater insight into the pathogenesis of systemic sclerosis-related calcinosis.
PURPOSE OF REVIEW: Calcinosis is a common complication of systemic sclerosis with no known effective pharmacologic therapy. We reviewed the literature regarding systemic sclerosis-related calcinosis as well as other disorders of biomineralization in order to identify targets of future study for calcinosis. RECENT FINDINGS:Patients with systemic sclerosis-related calcinosis demonstrate systemic abnormalities in mineralization pathways, including decreased levels of the mineralization inhibitor inorganic pyrophosphate. Insights from other mineralization disorders suggest that local and systemic phosphate metabolism pathways involving the ABCC6, ENPP1, and NT5E genes play a critical role in regulation of ectopic calcification. Knockout models of these genes may lead to an appropriate murine model for study of calcinosis. Poly(ADP-ribose) polymerase (PARP) enzymes may also play a critical role in hydroxyapatite nucleation and warrant future study in systemic sclerosis. Study of local and systemic mineralization pathways, particularly phosphate metabolism pathways and PARP enzymes, should provide greater insight into the pathogenesis of systemic sclerosis-related calcinosis.
Authors: Vivien M Hsu; Eszter Kozák; Qiaoli Li; Márta Bocskai; Naomi Schlesinger; Ann Rosenthal; Scott T McClure; László Kovács; László Bálint; Szilvia Szamosi; Gabriella Szücs; Mary Carns; Kathleen Aren; Isaac Goldberg; András Váradi; John Varga Journal: Rheumatology (Oxford) Date: 2022-03-02 Impact factor: 7.046