Distinctive Anabolic Roles Of 1,25-Dihydroxyvitamin D₃ In Teeth And Mandible Versus Long Bones

Elevated PTH in the secondary hyperparathyroidism of vitamin D deficiency is believed to be anabolic for long bones.We previously compared mice with targeted disruption of the gene encoding parathyroid hormone(PTH)(PTH^-/-mice)or the gene encoding 25 hydroxyvitamin D 1α-hydroxylase[1α(OH)ase][1α(OH)ase^-/-mice]with compound mutant PTH^-/-1α(OH)ase^-/-mice.We found that PTH plays a predominant role in appositional bone growth,whereas 1,25(OH)₂D₃ acts predominantly on endochondral bone formation in long bones.It is unknown,however, whether 1,25(OH)₂D₃ or PTH plays a role in dentin and dental alveolar bone formation in the mandibles as it does in long bones.To determine whether 1,25(OH)₂D plays a distinctive role in flat bones such as mandibles,we examined the effect of 1,25(OH)₂D₃ deficiency on dentin and dental alveolar bone formation and mineralization in the mandibles, and compared osteoblastic bone formation in the mandibles and tibiae in 1α(OH)ase^-/-mice.Compared to wild-type(WT)mice,the mineral density was decreased in the teeth and mandibles,and unmineralized dentin(predentin and biglycan immunopositive dentin)and unmineralized bone matrix in the dental alveolar bone were increased in 1α(OH)ase^-/-mice.The dental volume,reparative dentin volume and dentin sialoprotein immunopositive areas were reduced in 1α(OH)ase^-/- mice.The cortical thickness,dental alveolar bone volume and osteoblast numbers were all decreased significantly in the mandibles;in contrast,the osteoblast number and surface were increased in the trabecular bone of the tibiae in 1α(OH)ase^-/-mice consistent with their secondary hyperparathryoidism.The expression of parathyroid hormone receptor (PTHR)and insulin-like growth factor-1(IGF-1)was reduced slightly in mandibles,but enhanced in the long bones in the 1α(OH)ase^-/-mice. These results indicate that 1α,25(OH)₂D₃ plays distinct roles in dentin and dental alveolar bone formation in the mandibles relative to trabecular bone formation in long bones,and suggests that 1,25(OH)₂D₃ plays a more prominent anabolic role than does PTH in dentin and dental alveolar bone formation in mandibles.