| Summary: | 碩士 === 國防醫學院 === 生物及解剖學研究所 === 99 === Calcitonin (CT) is a 32-amino-acid peptide hormone that induces hypocalcemia by inhibiting osteoclast (OC) bone resorption and has therefore been clinically used to treat osteoporosis, hypercalcemia, and Paget's disease for nearly 30 years. But it is less widely used than other anti-bone resorption agents such as bisphosphonates (BPs). This is mostly because limited understanding of physiologic role of CT and little advances in study of the effects of CT on bone tissue. Recent studies have suggested that CT acts primarily to inhibit bone resorption, but the secondary inhibition of bone formation is less intense with CT than with BPs. Thus, CT treatment will lead to a continuously positive bone balance in contrast with other antiresorptive agents currently on the market and thereby, in a physiologic manner, result in improved bone quality. Though several lines of evidence indicate that CT inhibits OC apoptosis, the apoptotic signaling pathways regulated by CT in OCs remain to be elucidated. Sintered Dicalcium Pyrophosphate (SDCP) is newly developed BP type drug. SDCP could increase bone mass in ovariectomized rats. Since the two drugs inhibit osteoclasts via different mechanisms at the molecular level, the combined therapy may show an additive effect on bone. The purpose of this study were to study CT- and SDCP-induced signalings affect apoptosis in OCs and the therapeutic implication of combined treatment with CT and SDCP. The results from caspase 3 activity assay, annexin-V stain, and TUNEL showed that CT inhibits SDCP-induced apoptosis in OCs. Western blotting and pharmacological inhibition studies showed CT inhibits SDCP-induced OCs apoptosis by increasing the activity of Bcl-2 and Erk. TRAP stain analysis showed that CT inhibits SDCP-induced apoptosis, and therefore alleviates SDCP-induced decrease activity and survival of OCs. In the Osteopenic animal model, micro computed tomography analysis of the 5th lumbar vertebrate of ovariectomized rats showed combined therapy of CT and SDCP increases bone volume and decreased porosity. Serum bone marker analysis indicated that the synergistic effect may be due to decrease bone resorption and increase bone formation. In conclusion, CT treatment will lead to a positive bone balance in contrast with other antiresorptive agents currently on the market and thereby, in a physiologic manner, result in improved bone quality.
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