Calcium, Vitd Lack Of Bone Growth And Osteoblast Function And Mechanism

Calcium and vitamin D have long been known to play important roles in bone growth and development. Either calcium or vitamin D deficiency in children can induce bone growth disorders. However, the specific mechanisms in which calcium or vitamin D deficiency exerts on bone formation are still poorly understood. It is not clear whether the mechanisms of calcium deficiency and vitamin D deficiency on bone growth are any differences, whether their effects are mediated through direct actions on osteoblasts or how interference with osteoblast activity affects bone formation. To determine the mechanisms, we investigated the various bone and bone-related variables, including serum markers, histomorphometry, mineral composition. We also studied the expression pattern of mRNA levels for c-fos, c-jun, and vitamin D receptor content in relation to osteoblast phenotypic markers and osteoblast activities in young growing rats. 60 weaning male rats were randomized into four groups: group A(as control) fed diets with 0.5% calcium, 2000IUIkg vitamin D; group B(calcium deficiency)fed diets with 0.15% calcium, 2000IUIkg vitamin D; group C(vitamin D deficiency)fed diets with 0.5% calcium, without vitamin D; group D(both calcium and vitamin D deficiency) fed diets with 0.15% calcium, without vitamin D. One third of rats in each group were sacrificed at 0, 3, 6 week respectively. Results showed that serum Ca levels significantly decreased only in the C, D groups. The concentration of the 250HD3 increased as calcium deficiency developed and decreased over time in C and D groups. Calcium or vitamin D deficiency caused a dramatic rise in serum bone alkaline phosphatase activity and reduction in osteocalcin level. The tibia and femur length, fat-free dry bone weight, ash weight and mineral levels were also lower compared with those of corresponding controls. Histomorphormetry of proximal femur metaphysis revealed reductions in calcified trabucular bone volume. In addition, widening growth plate and chondrocytes disarrangement were documented in group C and D. The osteocalcin mRNA expression levels of osteoblast assayed by RT-PCR analysis showed that statistically significant decrease in B, C and D groups. The mRNA expressions of c-fos and c-jun gene were enhanced in group B and D, but remained unaltered in group C. The vitamin D receptor contents were lower in C, D groups without a change in receptor affinity. These studies demonstrated that calcium or vitamin D deficiency during the period of skeletal growth compromises both the quantity and quality of bone. Their impairments on bone formation and mineralization were mediated through osteoblast activity. Osteocalcin levels are closely correlated with bone formation and calcification. It also indicated that the mechanisms of down-regulation osteoblastic osteocalcin gene expressions in calcium or vitamin D deficiency were different. The calcium deficiency reduces the osteocalcin gene expression by enhancing the c-fos, c-jun mRNA expression in osteoblast, whereas the vitamin D deficiency results in a dramatic decrease in vitD receptor numbers that cause suppressions of osteocalcin gene expression.