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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林能裕(Neng-Yu Lin) | |
| dc.contributor.author | Hsuan-Yu Lin | en |
| dc.contributor.author | 林軒羽 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:31:46Z | - |
| dc.date.available | 2021-08-30 | |
| dc.date.available | 2022-11-24T03:31:46Z | - |
| dc.date.copyright | 2021-08-30 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-11 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81123 | - |
| dc.description.abstract | 骨質疏鬆症是一種慢性疾病，當骨吸收和骨沉積之間存在不平衡時就會發生。參考文獻指出，估計每年有超過2億人患有骨質疏鬆症。科學家們用兩種細胞類型監測這兩種活動：蝕骨細胞和成骨細胞，它們控制著骨骼的製造、維持和消耗。在典型的骨重塑週期中，成骨細胞調節骨吸收和骨沉積之間的平衡，並最終通過兩種蝕骨細胞激活細胞因子引起破骨細胞分化：巨噬細胞集落刺激因子 (MCSF) 和核因子κ-B配體受體激活劑(RANKL)。O-醣基化是必不可少的翻譯後修飾之一，對於蛋白質折疊、構造、分佈、穩定性及活性均有顯著影響，目前已在多種疾病中觀察到異常 O-醣基化的表達。GalNAcα1-O-Ser/Thr 糖肽 β3-半乳糖基轉移酶（C1GALT1）是負責正常組織中 O-醣基化成熟的酵素，此過程對細胞的物理及病理調節很重要，因此，我們旨在找出C1GALT1在蝕骨細胞生成中的作用。首先，RT-PCR 分析顯示在蝕骨細胞分化過程中C1galt1 及其分子伴侶C1galt1c1 (Cosmc) 的mRNA表現量降低。此外，在組織上透過TRAP染色發現去除C1galt1或使用 O-醣基化抑製劑來降低C1GALT1表現量，增強了蝕骨細胞分化。然而，來自電腦斷層掃描儀的骨體積和骨礦物質密度結果顯示蝕骨細胞生成對C1galt1被剔除之小鼠在卵巢切除模型中顯示相反的影響。我們接下來初步分析了C1galt1剔除蝕骨細胞中蝕骨細胞分化和骨吸收的相關基因，結果發現蝕骨細胞分化基因NFATc1和DC-STAMP增加，骨吸收活性基因TRAP在C1galt1 被踢除之蝕骨細胞中則下降。總而言之，C1GALT1的抑制可能會增加蝕骨細胞的分化，但會阻礙蝕骨細胞的骨吸收活動。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:31:46Z (GMT). No. of bitstreams: 1 U0001-1108202110040800.pdf: 2691721 bytes, checksum: dbe328406a5f4b8650ee129d116bda3e (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 致謝 i 中文摘要 ii Abstract iii Abbreviation iv CHAPTER ONE. Introduction 1 1.1 Question of interest 1 1.2. Bone homeostasis 2 1.2.1 Osteoporosis 2 1.2.2 Osteoblast differentiation and mechanism 3 1.2.3 Osteoclast differentiation and mechanism 5 1.2.4 Bone resorption 6 1.3 Glycosylation 7 1.3.1 Types of glycosylation 8 1.3.2 Mucin type O-glycosylation 9 CHAPTER TWO. Specific Aims and Hypothesis 13 CHAPTER THREE. Materials and Methods 14 3.1 Materials 14 3.1.1 RNA interference 14 3.1.2 Antibody 14 3.1.3 Primers 15 3.1.4 Chemical and Reagents 17 3.2 Method 19 3.2.1 Raw 264.7 culture 19 3.2.2 Osteoclast formation 19 3.2.3 Flow cytometry 20 3.2.4 Animal Handling 20 3.2.5 Tissue Decalcification 21 3.2.6 Immunohistochemical staining 21 3.2.7 Bone marrow isolation 22 3.2.8 Mouse primary osteoclast culture and stimulation 22 3.2.9 Virus infection 22 3.2.10 RNA extraction 23 3.2.11 RT-PCR 23 3.2.12 Quantitative real-time PCR 23 3.2.13 Western blot 24 3.2.14 Ovariectomy model 25 3.2.15 Micro computed tomography analysis 25 3.2.16 Statistical analysis 25 CHAPTER FOUR. RESULTS 26 4.1 Expression of O-glycosylation shows in big data analysis 26 4.2 VVA and PNA increase during osteoclast differentiation in pre-osteoclast 26 4.3 RANKL decreases the mRNA expression of C1galt1 and C1galt1c1 27 4.4 Inhibit O-glycosylation could increase osteoclasts differentiation 28 4.7 Bone volume increase in C1galt1 KO mice in myeloid cells in OVX model 31 CHAPTER FIVE. Discussion 32 5.1 Silencing C1GALT1 affect osteoclasts differentiation in vitro 32 5.2 C1GALT1 knockout may increase bone volume in postmenopausal women 33 CHAPTER SIX. Figures 34 References 48 圖目錄 (List of Figures) Figure 1. Mammalian protein O-glycosylation pathways. 12 Figure 2. GSEA software and reactome analysis 36 Figure 3. Flow cytometry on different lectins 38 Figure 4. Real-time analyze diagrams 39 Figure 5. Inhibit O-glycosylation by pharmacological ways 41 Figure 6. VVA increase in C1galt1 KO BMCs 42 Figure 7. The appearances on WT and C1GALT1 KO mice 44 Figure 8. The appearances on WT and C1GALT1 KO mice 46 Figure 9. Osteoclast markers analysis 47 表目錄 (List of Tables) Table 1. shRNA. 14 Table 2. Antibody 14 Table 3. Mouse primer 15 | |
| dc.language.iso | en | |
| dc.subject | 卵巢切除模型 | zh_TW |
| dc.subject | 骨質疏鬆 | zh_TW |
| dc.subject | 蝕骨細胞分化 | zh_TW |
| dc.subject | O型醣基化 | zh_TW |
| dc.subject | OVX model | en |
| dc.subject | Osteoclastogenesis | en |
| dc.subject | O-Glycosylation | en |
| dc.subject | C1GALT1 knockout | en |
| dc.title | 調控C1GALT1表現量在蝕骨細胞分化過程中所造成之影響 | zh_TW |
| dc.title | The Effect of C1GALT1 on Osteoclast Differentiation in vitro and in vivo | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 劉雅雯(Hsin-Tsai Liu),郭靜穎(Chih-Yang Tseng) | |
| dc.subject.keyword | 骨質疏鬆,蝕骨細胞分化,O型醣基化,卵巢切除模型, | zh_TW |
| dc.subject.keyword | Osteoclastogenesis,O-Glycosylation,C1GALT1 knockout,OVX model, | en |
| dc.relation.page | 55 | |
| dc.identifier.doi | 10.6342/NTU202102263 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-08-11 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 解剖學暨細胞生物學研究所 | zh_TW |
| 顯示於系所單位： | 解剖學暨細胞生物學科所 | |
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