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題 名 | Effects of Continuous Calcitonin Treatment on Osteoclasts Derived from Cocultures of Mouse Marrow Stromal and Spleen Cells=持續性抑鈣素刺激對源自於小鼠骨髓基質細胞與脾臟細胞共同培養之蝕骨細胞的影響 |
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作 者 | 劉步遠; 王拯宗; 呂娟馨; 江俊斌; 謝季全; 關學婉; | 書刊名 | 臺灣醫學會雜誌 |
卷 期 | 99:2 2000.02[民89.02] |
頁 次 | 頁140-150 |
分類號 | 415.148 |
關鍵詞 | 持續性抑鈣素; 小鼠; 骨髓基質細胞; 脾臟細胞; 蝕骨細胞; Calcitonin escape; Osteoclast; |
語 文 | 英文(English) |
英文摘要 | Background: Continuous calcitonin (CT) treatment for bone diseases associated with increased bone resorption may be followed by prolonged depression of osteoclast response to CT. The mechanisms of this "escape" phenomenon remain unclear. Methods: We examined the effects of continuous CT treatment on cell formation, calcitonin receptor (CTR) expression, response to CT, and bone resorption of osteoclasts in a coculture of mouse marrow stromal and spleen cells in the presence of 1,25-dihydroxyvitamin D □ [1,25(OH) □ D □ ]. Cells were cocultured and treated with salmon CT (sCT) for 7,14, or 21 days. The effects of continuous CT treatment on osteoclast formation was determined by quantitation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs). CTR expression in osteoclasts was determined by binding of [ □ I]sCT in autoradiography. Bone resorption and CT responsiveness were assessed by examining the formation of resorption pits and by enumerating osteoclast reattachment on dentine slices after sCT rechallenge. Results: TRAP-positive MNCs appeared in cocultures treated with sCT and were similar in number and morphology to those in control cultures, regardless of the concentration and duration of sCT treatment. A decrease in CTR expression was identified as a loss of silver grains from the TRAP-positive cells in cocultures receiving sCT treatment for 14 or 21 days. Partial recovery of CTR expression in TRAP-positive cells was evident in cocultures treated with sCT for only the first 7 days of coculture. TRAP-positi ve MNCs in cocultures treated with sCT for 14 or 21 days were resistant to the rechallenge with sCT. They attached to dentine slices and caused numerous resorption pits compared with control cells and cells treated with sCT for the first 7 days of coculture (p < 0.01). Conclusion: These findings suggest that the escape phenomenon that develops after continuous CT treatment may be due, at least in part to: 1) loss of responsiveness to CT in existing osteoclasts; and 2) development of new osteoclasts that are CTR-deficient and, therefore, refractory to CT rechallenge. |
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