Mechanisms involved in bone resorption regulated by vitamin D

Area of Science:

• Bone Biology and Metabolism
• Endocrinology
• Nutritional Science

Background:

• Active vitamin D (calcitriol) influences bone remodeling through the vitamin D receptor (VDR).
• Vitamin D's role in bone resorption appears concentration-dependent, with higher doses potentially suppressing it.
• Pharmacological vitamin D use in Japan increases bone mineral density (BMD) by reducing bone resorption.

Purpose of the Study:

• To investigate the specific roles of VDR in osteoblast-lineage cells and osteoclasts in vitamin D's effects on bone.
• To clarify whether VDR in osteoblasts or osteoclasts mediates the anti-resorptive effects of pharmacological vitamin D.
• To reconcile conflicting findings regarding vitamin D's dual actions on bone resorption.

Main Methods:

• Generation of osteoblast lineage-specific and osteoclast-specific VDR conditional knockout (cKO) mouse models.
• Utilized Osterix-Cre and Cathepsin K-Cre transgenic mice for targeted VDR deletion.
• Analyzed bone mineral density (BMD) and bone resorption in VDR cKO mice under different conditions.

Main Results:

• VDR in osteoblast-lineage cells or osteoclasts is not essential for bone resorption during homeostasis.
• VDR in osteoblast-lineage cells, but not osteoclasts, mediates the bone resorption suppression by pharmacological vitamin D.
• Comparison of different osteoblast-lineage VDR cKO models (Col1a1-VDR-cKO, Dmp1-VDR-cKO) revealed varied effects on bone mass.

Conclusions:

• Vitamin D's effect on bone resorption is context-dependent, involving VDR in osteoblast-lineage cells for anti-resorptive actions.
• The specific cell type expressing VDR and the vitamin D dosage protocol determine its net effect on bone.
• Further research is needed to fully elucidate the complex mechanisms of vitamin D in bone metabolism.