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Vitamin D and bone-How does vitamin D regulate bone formation and resorption?
- Source :
- Proceedings of the Japan Academy, Series B. 80:407-421
- Publication Year :
- 2004
- Publisher :
- Japan Academy, 2004.
-
Abstract
- Vitamin D was discovered as an anti-rachitic agent, but even at present, there is no direct evidence to support the concept that vitamin D directly stimulates osteoblastic bone formation and mineralization. It appears to be paradoxical, but vitamin D functions in the process of osteoclastic bone resorption. Osteoclasts, the only cells responsible for bone resorption, develop from hematopoietic cells of the monocyte-macrophage lineage. In 1992, we hypothesized that a membrane-bound factor, designated as "osteoclast differentiation factor (ODF)", is expressed on the plasma membrane of osteoblasts/stromal cells in response to osteotropic factors including the active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3]. Recently, four research groups including ours independently identified three key molecules (RANKL, RANK, and OPG) responsible for osteoclastogenesis. A long-sought-after ligand, ODF, was identical to RANKL. RANKL was a member of the membrane-associated TNF ligand family, which induced differentiation of spleen cells (osteoclast progenitors) into osteoclasts in the presence of M-CSF. RANK, a member of the TNF receptor family, was a signaling receptor essential for the RANKL-mediated osteoclastogenesis. OPG, a secreted member of the TNF receptor family, was a decoy receptor for RANKL. The discovery of RANKL, RANK and OPG opens a new era in the study of bone biology and the therapy of several metabolic bone diseases such as osteoporosis, rheumatoid arthritis, and periodontal diseases. (Communicated by Tadamitsu KISHIMOTO, M.J.A.)
- Subjects :
- musculoskeletal diseases
medicine.medical_specialty
Stromal cell
biology
Chemistry
Osteoporosis
General Physics and Astronomy
General Medicine
medicine.disease
Bone resorption
Resorption
medicine.anatomical_structure
Endocrinology
Osteoclast
RANKL
Internal medicine
medicine
Vitamin D and neurology
biology.protein
General Agricultural and Biological Sciences
Receptor
Subjects
Details
- ISSN :
- 13492896 and 03862208
- Volume :
- 80
- Database :
- OpenAIRE
- Journal :
- Proceedings of the Japan Academy, Series B
- Accession number :
- edsair.doi...........e93dab168be4a2d09c106add40911be1