Vitamin D receptor expression in mature osteoclasts reduces bone loss due to low dietary calcium intake in male mice.

Mature osteoclasts express the vitamin D receptor (VDR) and are able to respond to active vitamin D (1α, 25-dihydroxyvitamin D; 1,25(OH)D) by regulating cell maturation and activity. However, the in vivo consequences of vitamin D signalling directly within functionally mature osteoclasts is only partially understood. To investigate the in vivo role of VDR in mature osteoclasts, conditional deletion of the VDR under control of the cathepsin K promoter (Ctsk/Vdr), was assessed in 6 and 12-week-old mice, either under normal dietary conditions (NormCaP) or when fed a low calcium (0.

Absence of vitamin D receptor in mature osteoclasts results in altered osteoclastic activity and bone loss.

Mature osteoclasts express the vitamin D receptor (VDR) and are able to synthesise and respond to 1,25(OH)D via CYP27B1 enzyme activity. Whether vitamin D signalling within osteoclasts is necessary for the regulation of osteoclastic bone resorption in an in vivo setting is unclear. To determine the requirement for the VDR- and CYP27B1-mediated activity in mature osteoclasts, conditional deletion mouse models were created whereby either Vdr or Cyp27b1 gene was inactivated by breeding either Vdr or Cyp27b1 mice with Cathepsin K-Cre transgenic mice (Cstk) to generate Ctsk/Vdr and Ctsk/Cyp27b1 mice respectively.

Evidence for altered osteoclastogenesis in splenocyte cultures from VDR knockout mice.

The indirect action of 1α,25(OH)-vitamin-D (1,25D) on the osteoclast through stromal signalling is well established. The role of vitamin D in osteoclasts through direct 1,25D-VDR signalling is less well known. We showed previously that local 1,25D synthesis in osteoclasts modified osteoclastogenesis and osteoclastic resorptive activity.

Evidence for altered osteoclastogenesis in splenocyte cultures from Cyp27b1 knockout mice.

The association between increased serum 25-hydroxyvitamin D (25D) and reduced osteoclastic bone resorption is well known. Previously, we have demonstrated that mechanism by which this occurs, may include the conversion of 25D to 1,25-dihydroxyvitamin D (1,25D) by osteoclasts, catalysed by the CYP27B1 enzyme. Local 1,25D synthesis in osteoclasts was shown to regulate osteoclastogenesis and moderating resorptive activity.