1,25-dihydroxyvitamin D deficiency accelerates alveolar bone loss independent of aging and extracellular calcium and phosphorus

Background: Vitamin D is critical for bone homeostasis and immunomodulation. We therefore assessed whether 1,25-dihydroxyvitamin D (1,25(OH)(2)D) deficiency in mice with targeted deletion of the gene encoding 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha(OH)ase 1 alpha OH)ase(-/-) mice]) results in alveolar bone loss and periodontal inflammation in vivo. Methods: Ten-week-old and 12-month-old 1 alpha(OH)ase(-/-) mice and wild-type litter-mates were fed a normal diet or a rescue diet, and the phenotype of the periodontium was then analyzed using microcomputed tomography, histology, immunohistochemistry, and real-time Reverse transcription-polymerase chain reaction (RT-PCR). Results: Alveolar bone loss was increased and maxillary bone mineral density (BMD), osteoblast numbers, and the number of osterix-positive cells were decreased significantly in 1 alpha(OH)ase(-/-) mice compared with wild-type mice. Although aging from 10 weeks to 12 months accentuated these changes, and a rescue diet reduced them, the alterations in the 1 alpha(OH)ase(-/-) mice exceeded the effects of aging and diet change. Nuclear factor kappa light-chain-enhancer of activated B cells (NF-kappa B) p65 and CD3 positive cells, and the gene expression levels of interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, matrix metalloproteinase (MMP)-3 and -8 were all increased significantly in periodontal tissues of 1 alpha(OH)ase(-/-) mice compared with wild-type mice. Aging from 10 weeks to 12 months also accentuated these changes, and a rescue diet reduced them, however, the alterations in the 1 alpha(OH)ase(-/-) mice exceeded the effects of aging and diet change. Conclusion: 1,25(OH)(2)D deficiency in the 1 alpha(OH)ase(-/-) mice accelerated alveolar bone loss by inhibiting osteoblastic bone formation and enhancing periodontal tissue degeneration in a calcium- and phosphorus- as well as an age-independent manner.