脂肪所分泌的細胞激素Leptin在調節能量代謝和保護骨質方面有著關鍵角色。Leptin的失調與肥胖和骨質流失等狀況有關。研究指出，肥胖小鼠中Leptin上升與骨量增加呈正相關，而缺乏Leptin的小鼠則會出現顯著的骨質流失。然而，Leptin影響骨骼重塑的具體作用方式仍然無法完全解釋。另一方面，長期過度使用葡萄糖皮質激素（Glucocorticoids, GCs）是次發性骨質疏鬆症的常見原因之一。研究顯示，長期接觸地塞米松（DEX）導致粒線體功能損傷，從而引發成骨細胞死亡。過去的研究指出，GCs可讓成骨細胞的粒腺體功能產生雙相性變化，最初促進粒線體生成功能的上升，但隨著時間的增加，則會使粒線體的損傷增加並開啟細胞凋亡途徑。本研究旨在揭開Leptin和葡萄糖皮質激素之間的複雜交互作用，了解這些因子在骨代謝中的角色，並探索它們對骨健康的影響。透過分析Leptin對骨重塑和GCs對成骨細胞的作用，本研究將有助於開發與骨質疏鬆相關疾病的預防和治療方式。這些研究揭示了調節骨骼代謝的複雜機制，幫助我們了解激素及藥物因子對骨健康的不同影響。期望本研究能促進對骨代謝調控的深入理解，並為骨質疏鬆症和其他骨相關疾病的治療提供新的視角和研究方向。

Leptin, a hormone produced by fat cells, is crucial in regulating energy metabolism and maintaining bone quality. Dysregulation of leptin levels can lead to various health issues, including obesity and bone loss. Research indicates a complex relationship between leptin and bone health, where elevated leptin levels in obese individuals are often associated with increased bone mass, while mice deficient in leptin exhibit significant bone loss. Despite these observations, the specific mechanisms through which leptin influences bone remodeling remain inadequately defined. Conversely, excessive and long-term use of glucocorticoid is a common cause of secondary osteoporosis. Long-term exposure to glucocorticoids, such as dexamethasone, has been shown to impair mitochondrial function, ultimately resulting in osteoblast apoptosis. Studies have demonstrated that glucocorticoid treatment can induce biphasic changes in mitochondrial function within osteoblasts. Initially, these treatments promote mitochondrial biogenesis, enhancing mitochondrial activity. However, this benefit is often short-lived, as continued exposure leads to mitochondrial dysfunction and the activation of apoptotic pathways. These previous studies spell out the intricate regulatory pathways underlying bone metabolism and how various hormonal and pharmacological factors impact bone health. In this study, we aim to unravel the complexities of the interplay between leptin and glucocorticoids, focusing on their respective roles in osteoblast function and overall bone remodeling. By elucidating these interactions, we aspire to inform the growth of targeted treatment in bone-related diseases, particularly those associated with osteoporosis and glucocorticoid treatment. Understanding the regulatory roles of leptin and glucocorticoids in bone metabolism is vital for developing effective treatments for conditions such as osteoporosis. Our findings will contribute to the existing body of knowledge regarding hormonal interactions in bone health and the potential pathways for therapeutic advancement aimed at improving bone quality and preventing bone loss.

誌　　　謝 2
摘　　　要 3
ABSTRACT 4
LIST OF FIGURES 7
CHAPTER 1: INTRODUCTION 1
1.1 Background and Purpose 1
CHAPTER 2: LITERATURE REVIEW 5
2.1 Osteogenesis, and bone homeostasis 5
2.2 Glucocorticoids 7
2.3 Leptin 11
3.1 Osteoclast culture and differentiation 15
These detailed procedures outline the cultivation and differentiation in RAW 264.7 and MC3T3-E1 cells under specific conditions, setting the stage for investigating the impact of leptin on osteoclastogenesis and osteoblastogenesis. 15
Cell Lines and Culture Conditions 15
3.2 Tartrate-resistant acid phosphatase (TRAP) staining 16
3.3 Osteoblast culture and differentiation 18
3.4 MTT assay 19
3.5 Alkaline phosphtase (ALP) staining 20
3.6 Quantitative polymerase chain reaction (qPCR) 21
3.7 MitoTracker green stain and image analysis 24
3.8 Statistical analyses 25
CHAPTER 4: EXPERIMENTAL RESULTS AND DISCUSSION 26
4.1 Experimental Results 26
4.1.1 Leptin did not alter cell survival rate in osteoclast differentiation. 26
4.1.2 Leptin significantly increases inflammatory gene expression of Tnf-α and Nos2 in osteoclast. 27
4.1.3 Leptin does not affect osteoclast differentiation. 29
4.1.5 Short‑term dexamethasone treatment does not disrupt mitochondrial functions in the osteoblast. 33
4.1.6 Exogenous dexamethasone transiently upregulated mitochondrial bioactiviry in the osteoblast. 36
4.1.7 High level of dexamethasone mediates increases of mitochondrial contents in the osteoblast. 37
4.1.8 Dexamethasone treatment induces mitochondrial fusion subsequent to the elevation of mitochondrial biogenesis in osteoblasts. 40
4.1.9 Long‑term incubation of dexamethasone leads to mitochondrial fission for osteoblasts. 42
4.2 Discussion 45
CHAPTER 5: CONCLUSION 49
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