臺灣博碩士論文加值系統

　　骨質疏鬆症是因為骨再塑造失調，失去的骨量大於生成的骨量及骨置換率增加而造成。1995年本實驗室利用建立之大白鼠自然停經的動物模式，配合骨組織形態學法發現停經後大白鼠破骨細胞之活性和骨吸收面積明顯地增加以及鬆質骨大量地流失。雌激素缺乏進不僅會促使第一型介白質及第十一型介白質大量的分泌，並且增強其對破骨細胞之progenitor cells 及破骨細胞的影響。然而在自然停經後，破骨細胞形成及功能的實際變化情形至今仍不清楚。另外，雌激素缺乏後第一型及第十一型介白質大量的分泌，對破骨細胞之凋亡的實際影響情形並沒有文獻報導。本研究之目的旨在：1）配合實驗動物建立成年與停經期間大白鼠骨質密度測量模式，2）探討大白鼠停經後骨吸收作用（破骨細胞形成及功能)的改變情形，3）利用確立的造骨細胞與骨髓細胞共同培養模式，配合DAPI染色法、PI染色法、去氧核醣核酸斷裂分析法、破骨細胞Bc1-2蛋白質表現及流動細胞分析儀定量分析法評估破骨細胞形成後時間相關之細胞凋亡的情形和 4）探討第一型介白質和第十一型介白質對破骨細胞之凋亡的影響及其在停經後骨質流失上所可能扮演的角色。
　　本實驗結果發現：1）由雙能量X光骨質密度測定儀配合上小動物專用軟體建立了適合大白鼠骨質密度測量之模式，2）停經後大白鼠血清中骨吸收指標及破骨細胞腺核甘酸環化□產生有明顯上升之趨勢，3）雌激素缺乏之大白鼠其腰椎骨質密度有關明顯減少的趨勢，4）最適合研究破骨細胞形成、功能和細胞凋亡之ICR小白鼠造骨細胞與骨髓細胞共同培養研究模式已被確立，5）破骨細胞之凋亡是與時間及造骨細胞存在與否密切相關的和６）第一型和第十一型介白質明顯地抑制破骨細胞之凋亡。
　　本實驗結果顯示：1）適合大白鼠骨質密度測量之模式的建立有利於日後骨組織研究的進行，2）停經後大白鼠破骨細胞吸收參數明顯增加及骨質密度明顯下降，為導至停經後骨質流失之主要原因和　3）第一型和第十一型介白質可能經由明顯抑制破骨細胞之凋亡而在停經後骨質流失之發生機轉上扮演相當重要的角色。

　　Postmenopausal osteoporosis (PMO) is a disorder with high bone turnover characterized by imbalance between bone resorption and bone formation. Using menopausal animal model, it was noted that there were significant increase in bone resorption and decrease in trabecular bone volume by histomorphometry. However, the precise change in osteoclast formation and what role osteoclast apoptosis plays in postmenopausal osteopenia is unknown. Estrogen deficiency could upregulate not only the production of interleukin (IL)-1 and IL-11, but also the responsiveness of ostecoclast progenitors and ostecoclast. However. the precise changes in osteoclast formation and function after menopause is still unclear. In addition, there is no data available regarding whether an increase in secretion of IL -1 and IL-11 during estrogen deficiency will affect osteoclast apoptosis and cause subsequent osteopenia. Therefore, the purposes of this study were to 1) establish a reliable bone mineral density (BMD)measurement system for normal and climacteric rats. 2) investigate precise change of bone resorption (by serum bone resorption markers and cAMP production assay ) in climacteric rats, 3) evaluate time course of apoptotic changes in osteoclast (by DAPI staining, PI staining, DNA fragmentation, Bc1-2 expression and flow cytometric analysis) and 4) investigate effects of IL-1 adn IL-11 on osteoclast apoptosis and their possible roles in postmenopausal osteopenia. The results showed that 1) an available and reliable rat BMD measurement system was established for bone research, 2) serum biochemical bone resorption marker and osteoclast cAMP production were significantly increased after estrogen deficiency, 3) a significant decrease in BMD of rat lumbar vertebrae was noted after estrogen deficiency, 4) ICR mouse bone marrow cell-osteoblast co-culture system was more suitable for the study of osteoclast formation, function and apoptosis, 5) osteoclast apoptosis was time and osteoblast-related and 6) IL-1 and IL-11 potentially inhibited osteoclast apoptosis. The results of this study indicated that 1) an available and reliable rat BMD measurement system was established for bone research, 2) a significant increase in osteoclastic bone resorption and decrease in BMD after estrogen deficiency could mainly contribute to postmenopausal osteopenia, and 3) IL-1 and IL-11 may play an important role in the pathogenesis of postmenopausal osteopenia by potential inhibition of osteoclast apoptosis.