51. Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage.
- Author
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Gardiner EM, Baldock PA, Thomas GP, Sims NA, Henderson NK, Hollis B, White CP, Sunn KL, Morrison NA, Walsh WR, and Eisman JA
- Subjects
- Animals, Biomechanical Phenomena, Cell Lineage, Female, Mice, Mice, Transgenic, Tibia anatomy & histology, Tissue Distribution, Vitamin D analogs & derivatives, Vitamin D metabolism, Bone Resorption genetics, Osteoblasts metabolism, Osteogenesis genetics, Receptors, Calcitriol genetics
- Abstract
The microarchitecture of bone is regulated by complex interactions between the bone-forming and resorbing cells, and several compounds regulate both actions. For example, vitamin D, which is required for bone mineralization, also stimulates bone resorption. Transgenic mice overexpressing the vitamin D receptor solely in mature cells of the osteoblastic bone-forming lineage were generated to test the potential therapeutic value of shifting the balance of vitamin D activity in favor of bone formation. Cortical bone was 5% wider and 15% stronger in these mice due to a doubling of periosteal mineral apposition rate without altered body weight or calcium homeostatic hormone levels. A 20% increase in trabecular bone volume in transgenic vertebrae was also observed, unexpectedly associated with a 30% reduction in resorption surface rather than greater bone formation. These findings indicate anabolic vitamin D activity in bone and identify a previously unknown pathway from mature osteoblastic cells to inhibit osteoclastic bone resorption, counterbalancing the known stimulatory action through immature osteoblastic cells. A therapeutic approach that both stimulates cortical anabolic and inhibits trabecular resorptive pathways would be ideal for treatment of osteoporosis and other osteopenic disorders.
- Published
- 2000
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