Do Interactions of Vitamin D-3 and BMP Signaling Hold Implications in the Pathogenesis of Fibrodysplasia Ossificans Progressiva?

• Type of Material: Article
• Authors: Daniel Perrien, Emory University; Jessica L Pierce, Emory University
• Language: English
• Date: 2021-04-14
• Publisher: SPRINGER
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021, The Author(s), under exclusive licence to Springer Science Business Media, LLC, part of Springer Nature
• Final Published Version (URL): http://dx.doi.org/10.1007/s11914-021-00673-z
• Title of Journal or Parent Work: CURRENT OSTEOPOROSIS REPORTS
• Volume: 19
• Issue: 3
• Start Page: 358
• End Page: 367
• Grant/Funding Information: This publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R01AR073874 to DSP.
• Keywords: Chondrogenesis; Endocrinology & Metabolism; Science & Technology; Inflammation; Life Sciences & Biomedicine; ALK2; VDR; Muscle repair; Skeletal muscle

Abstract

Purpose of Review: Fibrodysplasia ossificans progressiva (FOP) is a debilitating rare disease known for episodic endochondral heterotopic ossification (HO) caused by gain-of-function mutations in ACVR1/ALK2. However, disease severity varies among patients with identical mutations suggesting disease-modifying factors, including diet, may have therapeutic implications. The roles of vitamin D3 in calcium metabolism and chondrogenesis are known, but its effects on BMP signaling and chondrogenesis are less studied. This review attempts to assess the possibility of vitamin D’s effects in FOP by exploring relevant intersections of VD3 with mechanisms of FOP flares. Recent Findings: In vitro and in vivo studies suggest vitamin D suppresses inflammation, while clinical studies suggest that vitamin D3 protects against arteriosclerosis and inversely correlates with non-genetic intramuscular HO. However, the enhancement of chondrogenesis, BMP signaling, and possibly Activin A expression by vitamin D may be more relevant in FOP. Summary: There appears to be little potential for vitamin D to reduce HO in FOP, but testing the potential for excess vitamin D to promote HO may be warranted.