Vitamin D and Bone: A Story of Endocrine and Auto/Paracrine Action in Osteoblasts

• Published in: Nutrients Vol. 15; no. 3; p. 480
• Main Authors: van Driel, Marjolein, van Leeuwen, Johannes P. T. M.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.01.2023; MDPI
• Subjects: Alfacalcidol; Apoptosis; Autocrine mechanisms; autocrine signaling; Bone and Bones - metabolism; bone formation; Bone remodeling; Calcifediol; Cytokines; enzymes; Extracellular matrix; Health aspects; Insulin; Insulin-like growth factors; Medical libraries; Metabolism; metabolites; Mineralization; Mixed Function Oxygenases - metabolism; Osteoblasts; Osteoblasts - metabolism; Phosphatase; Physiological aspects; Proteins; Receptors, Calcitriol - genetics; Review; Stem cells; transcription (genetics); Vitamin D; Vitamins - metabolism; Netherlands; differentiation and mineralization; vitamin D metabolism; bone; vitamin D receptor; osteoblasts
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15030480

Despite its rigid structure, the bone is a dynamic organ, and is highly regulated by endocrine factors. One of the major bone regulatory hormones is vitamin D. Its renal metabolite 1α,25-OH2D3 has both direct and indirect effects on the maintenance of bone structure in health and disease. In this review, we describe the underlying processes that are directed by bone-forming cells, the osteoblasts. During the bone formation process, osteoblasts undergo different stages which play a central role in the signaling pathways that are activated via the vitamin D receptor. Vitamin D is involved in directing the osteoblasts towards proliferation or apoptosis, regulates their differentiation to bone matrix producing cells, and controls the subsequent mineralization of the bone matrix. The stage of differentiation/mineralization in osteoblasts is important for the vitamin D effect on gene transcription and the cellular response, and many genes are uniquely regulated either before or during mineralization. Moreover, osteoblasts contain the complete machinery to metabolize active 1α,25-OH2D3 to ensure a direct local effect. The enzyme 1α-hydroxylase (CYP27B1) that synthesizes the active 1α,25-OH2D3 metabolite is functional in osteoblasts, as well as the enzyme 24-hydroxylase (CYP24A1) that degrades 1α,25-OH2D3. This shows that in the past 100 years of vitamin D research, 1α,25-OH2D3 has evolved from an endocrine regulator into an autocrine/paracrine regulator of osteoblasts and bone formation.