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

• Authors: Daniel Perrien, Emory University; Jessica L Pierce, Emory University
• Journal Title: CURRENT OSTEOPOROSIS REPORTS
• Volume: Volume 19, Number 3
• Publisher: SPRINGER | 2021-04-14, Pages 358-367
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1007/s11914-021-00673-z
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Endocrinology & Metabolism; VDR; Inflammation; ALK2; Muscle repair; Skeletal muscle; Chondrogenesis

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.