RESPONSIVENESS OF GENE-EXPRESSION MARKERS OF OSTEOBLASTIC AND OSTEOCLASTIC ACTIVITY TO CALCITONIN IN THE APPENDICULAR AND AXIAL SKELETON OFTHE RAT IN-VIVO

We have previously shown that calcitonin (CT), an inhibitor of bone re sorption, increases vertebral, but not femoral bone density in the rat [3]. To address the physiologic responses associated with these effec ts on bone mineral density (BMD), we assessed mRNA transcripts reflect ing activities of osteoblasts (type I collagen, osteocalcin, osteopont in, and alkaline phosphatase), osteoclasts [tartrate-resistant acid ph osphatase (TRAP)], and cell proliferation (histone H4) in the spine an d femur of these rats. CT increased spine BMD while increasing type I collagen and decreasing TRAP and histone mRNAs. In the femur, where CT had no effect on BMD, it decreased type I collagen and histone H-4 mR NA but did not affect TRAP. CT had no effect on the gene expression of osteocalcin, osteopontin, or alkaline phosphatase at either site. The results indicate that selective alterations in gene expression, as re flected by steady state mRNA levels, are consistent with the changes o bserved by BMD measurement, and can more clearly define the specific c ontribution from osteoblast and osteoclast activity. This study demons trates a heterogeneity in response of the axial and appendicular skele ton to CT, reflected by alterations in gene expression that provide a basis for understanding the observed BMD responses to various pharmaco logic interventions.