Poster Presentation 6th Australian Health and Medical Research Congress 2012

Dietary calcium-mediated changes to circulating 1,25D levels arbitrate anabolic or anti-anabolic activities in Vitamin D Receptor over-expressed in mature osteoblasts mouse model (OSVDR mice). (#477)

Rahma Triliana 1 2 , Nga L Lam 1 3 , Peter D O’Loughlin 1 2 , Howard A Morris 1 2 3 4 , Paul H Anderson 1 3 4
  1. Musculoskeletal Biology Research, Chemical Pathology, SA Pathology, Adelaide, SA, Australia
  2. School of Medicine , University of Adelaide, Adelaide, SA, Australia
  3. School of Medical Sciences, University Of Adelaide, Adelaide, SA, Australia
  4. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide,, SA, Australia

The response to direct activity of vitamin D within bone forming osteoblasts is unclear, with reports of inhibition and stimulation of mineralisation as well as indirect effects of bone resorption. The transgenic over-expression of human vitamin D receptor in mature osteoblasts in a mouse (OSVDR mice) demonstrate increased cortical and trabecular bone due to increased bone formation rate (BFR) as well as reduced osteoclast activity. While this anabolic activity is observed when the dietary calcium intake is adequate, it is unclear whether OSVDR mice can maintain this bone phenotype when fed a low dietary calcium level causing plasma 1,25D levels to rise. To answer this question, six-week-old female OSVDR and WT mice were fed either a 1% Ca (HCa) diet or a moderately low 0.1% Ca (LCa) diet for 4 months. At time of death, mean serum 1,25D levels in LCa OSVDR mice were 1.8-fold higher than HCa OSVDR mice (P<0.01). HCa OSVDR mice exhibit increases in tibial metaphyseal bone volume (12%, P<0.05) and cortical bone volume (15% P<0.01) compared to WT, consistent with previous observations. In contrast, LCa OSVDR exhibit diminished bone volume both in the tibial metaphysis and cortical bone volume, which was comparable to levels in WT mice. The reduction in bone volume in LCa OSVDR mice compared to HCa OSVDR mice occurred without a rise in RANKL-mediated osteoclastogenesis or resorption. In contrast, in LCa OSVDR mice, BFR and mRNA levels for osteoblastic genes Runx2, ALP, Col1, Dmp1 and osteocalcin were all markedly lower compared to all other groups (P<0.01). Thus, the diminished bone volume in LCa OSVDR was due to a failure in bone formation. These data suggest that in the presence of low dietary calcium and high circulating 1,25D levels, inappropriately low bone resorption and bone formation occurs resulting in reduced bone volume.