Bone biochemistry and physiology from the perspectives of the vitamin D endocrine system

Vitamin D plays an indispensable role in the dual processes of bone formation (mediated by osteoblasts) and bone resorption (mediated by osteoclasts). More recently, researchers have confirmed the existence of a vitamin D endocrine system, which is responsible for describing the "sphere of biological influence" of vitamin D3. In that system, the kidney serves as the endocrine gland that produces 1,25-dihydroxyvitamin D3. This hormonally active form of vitamin D3 generates many, if not all, of the biologic responses attributed to the parent vitamin D3, including its role in bone formation and bone resorption. In addition, 1,25-dihydroxyvitamin D3 is able to generate biologic responses via both genomic and nongenomic pathways. The classic nuclear receptor for 1,25-dihydroxyvitamin D3 is present in more than 30 target tissues. This paper reviews evidence for the critical role of 1,25-dihydroxyvitamin D3 in cell differentiation, particularly of hematopoietic cells, as well as in the generation of the bone resorptive cell--the osteoclast. In the past year, much evidence has been accumulated supporting the claim that 1,25-dihydroxyvitamin D3 tightly regulates differentiation of osteoclast progenitors into osteoclasts. Osteoclast progenitors are believed to be derived from the monocyte-macrophage lineage. However, the generation of new osteoclasts is modulated by osteoblastic stromal cells, which are one of the target cells for the nuclear actions of 1,25-dihydroxyvitamin D3.