CALCIUM OR VITAMIN
D DEFICIENCY IN YOUNG GROWING RATS IMPAIRS SKELETAL DEVELOPMENT THROUGH
EFFECTS ON OSTEOBLAST GENE EXPRESSION
Wang H, Li HQ, Yang XQ
Children's Hospital, Chongqing University of
Medical Sciences, China
Objective: To investigate the
effect and mechanism of calcium or vitamin D deficiency on bone formation
through its direct actions on osteoblasts.
Methods: Four groups of fifteen
weaning male rats were fed adequate(0.5% calcium, 2000IU/Kg vitD, control),
calcium deficient(0.15% calcium, 2000IU/Kg vitD, CD), vitamin D
deficient(0.5% calcium, without vitD, VDD) or both calcium and vitamin D
deficient(0.15% calcium, without vitD, CDD) diets for six week. One third
of rats in each group were sacrificed at 0, 3, 6 week respectively. The effects
of calcium or vitamin D deficiency on skeletal development were examined by
bone biochemical marker analysis, bone growth and mineral content
determination, bone histomorphormetry, osteoblast gene expression for
osteocalcin, c-fos, c-jun, and vitamin D receptor scatchard analysis.
Results: In CD, VDD, CDD rats,
serum bone ALP activity was significantly elevated and serum osteocalcin
levels decreased. At the same time, femur and tibia length, fat-free dry
bone weight, ash weight were reduced. All measured bone mineral levels were
also lower, except for potassium. Image analysis of sections of the
proximal femur metaphysis revealed reductions in calcified trabucular bone
volume. VDD and CDD rats showed a thicker epiphyseal growth plate, abundant
osteoid and irregularity of the provisional zone of calcification.
Osteoblast osteocalcin mRNA expression levels in all groups were
significantly reduced. In CD and CDD rats, c-fos, c-jun gene expression was
increased, whereas VDD and CDD reduced 1,25 (OH)2D3
receptor number in osteoblast without a change in the receptor affinity.
Conclusion: Calcium or vitamin D
deficiency during the period of skeletal growth compromises both the
quantity and quality of bone mediated through effects on osteoblasts.