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

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 1 alpha,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 1 alpha,25-OH2D3 to ensure a direct local effect. The enzyme 1 alpha-hydroxylase (CYP27B1) that synthesizes the active 1 alpha,25-OH2D3 metabolite is functional in osteoblasts, as well as the enzyme 24-hydroxylase (CYP24A1) that degrades 1 alpha,25-OH2D3. This shows that in the past 100 years of vitamin D research, 1 alpha,25-OH2D3 has evolved from an endocrine regulator into an autocrine/paracrine regulator of osteoblasts and bone formation.

Automated summary

Despite its rigid structure, the bone is a dynamic organ, highly regulated by endocrine factors. Vitamin D, particularly its renal metabolite 1 alpha,25-OH2D3, plays a major role in maintaining bone structure by influencing osteoblasts in various ways. These include directing osteoblasts towards proliferation or apoptosis, regulating their differentiation and bone matrix production, and controlling the mineralization of the bone matrix. Osteoblasts also possess the enzymes necessary to metabolize 1 alpha,25-OH2D3, indicating the transition of vitamin D from an endocrine regulator to an autocrine/paracrine regulator in bone formation.