請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73008
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 吳信志(SHINN-CHIH WU) | |
dc.contributor.author | Yu-Hsu Chen | en |
dc.contributor.author | 陳俞旭 | zh_TW |
dc.date.accessioned | 2021-06-17T07:13:41Z | - |
dc.date.available | 2020-07-25 | |
dc.date.copyright | 2019-07-25 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-07-16 | |
dc.identifier.citation | 1.Vandewalle, J., et al., Therapeutic Mechanisms of Glucocorticoids. Trends Endocrinol Metab, 2018. 29(1): p. 42-54.
2.Pazirandeh, A., et al., Effects of altered glucocorticoid sensitivity in the T cell lineage on thymocyte and T cell homeostasis. FASEB J, 2002. 16(7): p. 727-9. 3.de Quervain, D.J., B. Roozendaal, and J.L. McGaugh, Stress and glucocorticoids impair retrieval of long-term spatial memory. Nature, 1998. 394(6695): p. 787-90. 4.Lupien, S.J., et al., Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci, 2009. 10(6): p. 434-45. 5.Liu, C., et al., Inhibition of dehydration-induced water intake by glucocorticoids is associated with activation of hypothalamic natriuretic peptide receptor-A in rat. PLoS One, 2010. 5(12): p. e15607. 6.Liu, C., et al., Glucocorticoids improve renal responsiveness to atrial natriuretic peptide by up-regulating natriuretic peptide receptor-A expression in the renal inner medullary collecting duct in decompensated heart failure. J Pharmacol Exp Ther, 2011. 339(1): p. 203-9. 7.Schacke, H., W.D. Docke, and K. Asadullah, Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther, 2002. 96(1): p. 23-43. 8.Overman, R.A., J.Y. Yeh, and C.L. Deal, Prevalence of oral glucocorticoid usage in the United States: a general population perspective. Arthritis Care Res (Hoboken), 2013. 65(2): p. 294-8. 9.De Vries, F., et al., Fracture risk with intermittent high-dose oral glucocorticoid therapy. Arthritis Rheum, 2007. 56(1): p. 208-14. 10.Wu, Z., N.L. Bucher, and S.R. Farmer, Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids. Mol Cell Biol, 1996. 16(8): p. 4128-36. 11.Weinstein, R.S., et al., Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest, 1998. 102(2): p. 274-82. 12.Ohnaka, K., et al., Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts. Biochem Biophys Res Commun, 2005. 329(1): p. 177-81. 13.Sato, A.Y., et al., Protection From Glucocorticoid-Induced Osteoporosis by Anti-Catabolic Signaling in the Absence of Sost/Sclerostin. J Bone Miner Res, 2016. 31(10): p. 1791-1802. 14.Swanson, C., et al., Glucocorticoid regulation of osteoclast differentiation and expression of receptor activator of nuclear factor-kappaB (NF-kappaB) ligand, osteoprotegerin, and receptor activator of NF-kappaB in mouse calvarial bones. Endocrinology, 2006. 147(7): p. 3613-22. 15.Hofbauer, L.C., et al., Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology, 1999. 140(10): p. 4382-9. 16.Mazziotti, G., et al., Glucocorticoid-induced osteoporosis: pathophysiological role of GH/IGF-I and PTH/VITAMIN D axes, treatment options and guidelines. Endocrine, 2016. 54(3): p. 603-611. 17.Mandal, C.C., et al., Reactive oxygen species derived from Nox4 mediate BMP2 gene transcription and osteoblast differentiation. Biochem J, 2011. 433(2): p. 393-402. 18.Callaway, D.A. and J.X. Jiang, Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases. J Bone Miner Metab, 2015. 33(4): p. 359-70. 19.Atashi, F., A. Modarressi, and M.S. Pepper, The role of reactive oxygen species in mesenchymal stem cell adipogenic and osteogenic differentiation: a review. Stem Cells Dev, 2015. 24(10): p. 1150-63. 20.Almeida, M., et al., Glucocorticoids and tumor necrosis factor alpha increase oxidative stress and suppress Wnt protein signaling in osteoblasts. J Biol Chem, 2011. 286(52): p. 44326-35. 21.Flaherty, R.L., et al., Glucocorticoids induce production of reactive oxygen species/reactive nitrogen species and DNA damage through an iNOS mediated pathway in breast cancer. Breast Cancer Res, 2017. 19(1): p. 35. 22.Wallerath, T., et al., Down-regulation of the expression of endothelial NO synthase is likely to contribute to glucocorticoid-mediated hypertension. Proc Natl Acad Sci U S A, 1999. 96(23): p. 13357-62. 23.Sionov, R.V., et al., Glucocorticoid-induced apoptosis revisited: a novel role for glucocorticoid receptor translocation to the mitochondria. Cell Cycle, 2006. 5(10): p. 1017-26. 24.Koufali, M.M., et al., The dynamic localization of the glucocorticoid receptor in rat C6 glioma cell mitochondria. Mol Cell Endocrinol, 2003. 209(1-2): p. 51-60. 25.Moutsatsou, P., et al., Localization of the glucocorticoid receptor in rat brain mitochondria. Arch Biochem Biophys, 2001. 386(1): p. 69-78. 26.Tissing, W.J., et al., Molecular determinants of glucocorticoid sensitivity and resistance in acute lymphoblastic leukemia. Leukemia, 2003. 17(1): p. 17-25. 27.Boumpas, D.T., et al., Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. 1993. 119(12): p. 1198-1208. 28.Hartmann, K., et al., Molecular actions of glucocorticoids in cartilage and bone during health, disease, and steroid therapy. 2016. 96(2): p. 409-447. 29.Rhen, T. and J.A.J.N.E.J.o.M. Cidlowski, Antiinflammatory action of glucocorticoids—new mechanisms for old drugs. 2005. 353(16): p. 1711-1723. 30.Vandevyver, S., et al., New insights into the anti-inflammatory mechanisms of glucocorticoids: an emerging role for glucocorticoid-receptor-mediated transactivation. 2013. 154(3): p. 993-1007. 31.Schäcke, H., et al., Mechanisms involved in the side effects of glucocorticoids. 2002. 96(1): p. 23-43. 32.McDonough, A.K., J.R. Curtis, and K.G.J.C.o.i.r. Saag, The epidemiology of glucocorticoid-associated adverse events. 2008. 20(2): p. 131-137. 33.Seibel, M.J., et al., Glucocorticoid-induced osteoporosis: mechanisms, management, and future perspectives. 2013. 1(1): p. 59-70. 34.Gruver-Yates, A.L. and J.A.J.C. Cidlowski, Tissue-specific actions of glucocorticoids on apoptosis: a double-edged sword. 2013. 2(2): p. 202-223. 35.Zhou, H., M.S. Cooper, and M.J.J.B.r. Seibel, Endogenous glucocorticoids and bone. 2013. 1: p. 107. 36.Hachemi, Y., et al., Molecular mechanisms of glucocorticoids on skeleton and bone regeneration after fracture. 2018. 61(1): p. R75-R90. 37.Moghadam‐Kia, S. and V.P.J.I.j.o.d. Werth, Prevention and treatment of systemic glucocorticoid side effects. 2010. 49(3): p. 239-248. 38.Shi, X.-M., et al., Mechanism of glucocorticoid-induced osteoporosis: an update, in Glucocorticoids-New Recognition of Our Familiar Friend. 2012, Intech. 39.Sarinho, E.S.C. and V.M.P.P.J.R.P.d.P. Melo, Glucocorticoid-induced bone disease: mechanisms and importance in pediatric practice. 2017. 35(2): p. 207-215. 40.Fraser, L.-A. and J.D.J.T.a.i.m.d. Adachi, Glucocorticoid-induced osteoporosis: treatment update and review. 2009. 1(2): p. 71-85. 41.Hsu, E., M.J.C.o.i.e. Nanes, diabetes,, and obesity, Advances in treatment of glucocorticoid-induced osteoporosis. 2017. 24(6): p. 411-417. 42.Buehring, B., et al., Glucocorticoid-induced osteoporosis: an update on effects and management. 2013. 132(5): p. 1019-1030. 43.Cosman, F., et al., Clinician’s guide to prevention and treatment of osteoporosis. 2014. 25(10): p. 2359-2381. 44.Romas, E.J.A.p., Corticosteroid-induced osteoporosis and fractures. 2008. 31(2): p. 45-9. 45.Kling, J.M., B.L. Clarke, and N.P.J.J.o.w.s.h. Sandhu, Osteoporosis prevention, screening, and treatment: a review. 2014. 23(7): p. 563-572. 46.Johnson, T.E., et al., Thiazolidinedione effects on glucocorticoid receptor-mediated gene transcription and differentiation in osteoblastic cells. 1999. 140(7): p. 3245-3254. 47.Zhang, W., N. Yang, and X.-M.J.J.o.B.C. Shi, Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid-induced leucine zipper (GILZ). 2008. 283(8): p. 4723-4729. 48.Jeon, M.J., et al., Activation of peroxisome proliferator-activated receptor-γ inhibits the Runx2-mediated transcription of osteocalcin in osteoblasts. 2003. 278(26): p. 23270-23277. 49.Rauch, A., et al., Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor. 2010. 11(6): p. 517-531. 50.Almeida, M., et al., Glucocorticoids and tumor necrosis factor (TNF) α increase oxidative stress and suppress WNT signaling in osteoblasts. 2011: p. jbc. M111. 283481. 51.Feng, Y.-L. and X.-L.J.C.-b.i. Tang, Effect of glucocorticoid-induced oxidative stress on the expression of Cbfa1. 2014. 207: p. 26-31. 52.Ding, L.-Z., et al., Mangiferin inhibits apoptosis and oxidative stress via BMP2/Smad-1 signaling in dexamethasone-induced MC3T3-E1 cells. 2018. 41(5): p. 2517-2526. 53.Hou, G.-Q., et al., Lipopolysaccharide (LPS) promotes osteoclast differentiation and activation by enhancing the MAPK pathway and COX-2 expression in RAW264. 7 cells. 2013. 32(2): p. 503-510. 54.Han, D., et al., P21 Waf1/Cip1 depletion promotes dexamethasone-induced apoptosis in osteoblastic MC3T3-E1 cells by inhibiting the Nrf2/HO-1 pathway. 2018. 92(2): p. 679-692. 55.Guntur, A.R., et al., Osteoblast‐like MC3T3‐E1 Cells Prefer Glycolysis for ATP Production but Adipocyte‐like 3T3‐L1 Cells Prefer Oxidative Phosphorylation. 2018. 56.Weijtens, O., et al., High concentration of dexamethasone in aqueous and vitreous after subconjunctival injection. 1999. 128(2): p. 192-197. 57.Ding, L.Z., et al., Mangiferin inhibits apoptosis and oxidative stress via BMP2/Smad-1 signaling in dexamethasone-induced MC3T3-E1 cells. Int J Mol Med, 2018. 41(5): p. 2517-2526. 58.Owen, R. and G.C. Reilly, In vitro Models of Bone Remodelling and Associated Disorders. Front Bioeng Biotechnol, 2018. 6: p. 134. 59.Du, J., et al., Dynamic regulation of mitochondrial function by glucocorticoids. Proc Natl Acad Sci U S A, 2009. 106(9): p. 3543-8. 60.Ott, M., et al., Mitochondria, oxidative stress and cell death. Apoptosis, 2007. 12(5): p. 913-22. 61.You, J.M., et al., Mechanism of glucocorticoid-induced oxidative stress in rat hippocampal slice cultures. Can J Physiol Pharmacol, 2009. 87(6): p. 440-7. 62.Zhou, W., et al., Toxoplasma gondii Proliferation Require Down-Regulation of Host Nox4 Expression via Activation of PI3 Kinase/Akt Signaling Pathway. PLoS One, 2013. 8(6): p. e66306. 63.Bera, S., et al., Dexamethasone-induced oxidative stress enhances myeloma cell radiosensitization while sparing normal bone marrow hematopoiesis. 2010. 12(12): p. 980-992. 64.Qiao, S., S. Okret, and M.J.E. Jondal, Thymocyte-synthesized glucocorticoids play a role in thymocyte homeostasis and are down-regulated by adrenocorticotropic hormone. 2009. 150(9): p. 4163-4169. 65.Behl, C., et al., Glucocorticoids enhance oxidative stress-induced cell death in hippocampal neurons in vitro. 1997. 138(1): p. 101-106. 66.Iuchi, T., et al., Glucocorticoid excess induces superoxide production in vascular endothelial cells and elicits vascular endothelial dysfunction. 2003. 92(1): p. 81-87. 67.Khanduja, K.L., et al., Corticosteroids affect nitric oxide generation, total free radicals production, and nitric oxide synthase activity in monocytes of asthmatic patients. 2011. 346(1-2): p. 31-37. 68.Takuma, A., et al., Dexamethasone enhances osteoclast formation synergistically with transforming growth factor-ß by stimulating the priming of osteoclast progenitors for differentiation into osteoclasts. 2003. 69.Kearns, A.E., S. Khosla, and P.J.J.E.r. Kostenuik, Receptor activator of nuclear factor κB ligand and osteoprotegerin regulation of bone remodeling in health and disease. 2007. 29(2): p. 155-192. 70.Sivagurunathan, S., et al., Influence of glucocorticoids on human osteoclast generation and activity. 2005. 20(3): p. 390-398. 71.Jia, D., et al., Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density. 2006. 147(12): p. 5592-5599. 72.Maio, R., et al., Oxidative stress impairs endothelial function in nondipper hypertensive patients. 2012. 30(2): p. 85-92. 73.Sato, H., et al., Glucocorticoid generates ROS to induce oxidative injury in the hippocampus, leading to impairment of cognitive function of rats. 2010. 47(3): p. 224-232. 74.Datta, H., et al., The cell biology of bone metabolism. 2008. 61(5): p. 577-587. 75.Siddiqui, J.A. and N.C.J.P. Partridge, Physiological bone remodeling: systemic regulation and growth factor involvement. 2016. 31(3): p. 233-245. 76.Seibel, M.J., M.S. Cooper, and H. Zhou, Glucocorticoid-induced osteoporosis: mechanisms, management, and future perspectives. The lancet Diabetes & endocrinology, 2013. 1(1): p. 59-70. 77.Johnson, T.E., et al., Thiazolidinedione effects on glucocorticoid receptor-mediated gene transcription and differentiation in osteoblastic cells. Endocrinology, 1999. 140(7): p. 3245-3254. 78.Zhang, W., N. Yang, and X.-M. Shi, Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid-induced leucine zipper (GILZ). Journal of Biological Chemistry, 2008. 283(8): p. 4723-4729. 79.Jeon, M.J., et al., Activation of peroxisome proliferator-activated receptor-γ inhibits the Runx2-mediated transcription of osteocalcin in osteoblasts. Journal of Biological Chemistry, 2003. 278(26): p. 23270-23277. 80.Almeida, M., et al., Glucocorticoids and tumor necrosis factor α increase oxidative stress and suppress Wnt protein signaling in osteoblasts. Journal of Biological Chemistry, 2011. 286(52): p. 44326-44335. 81.Feng, Y.-L. and X.-L. Tang, Effect of glucocorticoid-induced oxidative stress on the expression of Cbfa1. Chemico-biological interactions, 2014. 207: p. 26-31. 82.Yamada, M., et al., N-acetyl cysteine as an osteogenesis-enhancing molecule for bone regeneration. Biomaterials, 2013. 34(26): p. 6147-6156. 83.Saklatvala, J., Glucocorticoids: do we know how they work? Arthritis Research & Therapy, 2002. 4(3): p. 146. 84.Yudt, M.R. and J.A. Cidlowski, The glucocorticoid receptor: coding a diversity of proteins and responses through a single gene. Molecular endocrinology, 2002. 16(8): p. 1719-1726. 85.Chen, Y.-H., et al., Different susceptibilities of osteoclasts and osteoblasts to glucocorticoid-induced oxidative stress and mitochondrial alterations. Chinese Journal of Physiology, 2019. 62(2): p. 70. 86.De Bosscher, K., vanden Berghe W, Haegeman G. The interplay between the glucocorticoid receptor and nuclear factor-κB or activator protein-1: molecular mechanisms for gene repression. Endocr Rev, 2003. 24(4): p. 488-522. 87.Lemberger, T., et al., Regulation of the peroxisome proliferator-activated receptor alpha gene by glucocorticoids. Journal of Biological Chemistry, 1994. 269(40): p. 24527-24530. 88.Löwenberg, M., et al., Glucocorticoids cause rapid dissociation of a T‐cell‐receptor‐associated protein complex containing LCK and FYN. EMBO reports, 2006. 7(10): p. 1023-1029. 89.Bartis, D., et al., Intermolecular relations between the glucocorticoid receptor, ZAP-70 kinase, and Hsp-90. Biochemical and biophysical research communications, 2007. 354(1): p. 253-258. 90.Sionov, R.V., et al., Role of mitochondrial glucocorticoid receptor in glucocorticoid-induced apoptosis. Journal of Experimental Medicine, 2006. 203(1): p. 189-201. 91.Talabér, G., et al., Mitochondrial translocation of the glucocorticoid receptor in double-positive thymocytes correlates with their sensitivity to glucocorticoid-induced apoptosis. International immunology, 2009. 21(11): p. 1269-1276. 92.Du, J., B. McEwen, and H.K. Manji, Glucocorticoid receptors modulate mitochondrial function: A novel mechanism for neuroprotection. Communicative & integrative biology, 2009. 2(4): p. 350-352. 93.Liang, B., et al., Integrinβ6-targeted immunoliposomes mediate tumor-specific drug delivery and enhance therapeutic efficacy in colon carcinoma. Clinical Cancer Research, 2015. 21(5): p. 1183-1195. 94.Wang, H., et al., The metabolic function of cyclin D3–CDK6 kinase in cancer cell survival. Nature, 2017. 546(7658): p. 426. 95.Le, P.P., et al., Glucocorticoid receptor-dependent gene regulatory networks. PLoS genetics, 2005. 1(2): p. e16. 96.Kelly, D.P. and R.C. Scarpulla, Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes & development, 2004. 18(4): p. 357-368. 97.Jornayvaz, F.R. and G.I. Shulman, Regulation of mitochondrial biogenesis. Essays in biochemistry, 2010. 47: p. 69-84. 98.Kowald, A. and T.B. Kirkwood, Evolution of the mitochondrial fusion–fission cycle and its role in aging. Proceedings of the National Academy of Sciences, 2011. 108(25): p. 10237-10242. 99.Ventura-Clapier, R., A. Garnier, and V. Veksler, Transcriptional control of mitochondrial biogenesis: the central role of PGC-1α. Cardiovascular research, 2008. 79(2): p. 208-217. 100.Youle, R.J. and A.M. Van Der Bliek, Mitochondrial fission, fusion, and stress. Science, 2012. 337(6098): p. 1062-1065. 101.Hirayama, T., A. Sabokbar, and N. Athanasou, Effect of corticosteroids on human osteoclast formation and activity. Journal of endocrinology, 2002. 175(1): p. 155-164. 102.Hamouda, S. and A. Yasear, Effect of dexamethasone on osteoclast formation in the alveolar bone of rabbits. Iraqi Journal of Veterinary Sciences, 2009. 23(1): p. 13-16. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73008 | - |
dc.description.abstract | 葡萄糖皮質素所引起的骨質流失,是常見的後天骨鬆的類型,也是造成年輕人骨鬆的重要成因。在骨骼新陳代謝中,高劑量葡萄糖皮質素會造成成骨細胞與骨細胞凋亡而引發骨質流失。根據先前的研究,成骨細胞與骨細胞的凋亡可能為氧化壓力所導致,但是其中的機制並不完全清楚。且葡萄糖皮質素是否也會對蝕骨細胞造成氧化壓力也還沒有定論。在本論文的第一部分研究中,我們觀察到隨著葡萄糖皮質素劑量增加和培養時間增加,氧化壓力也隨之上升,造成成骨細胞凋亡,粒線體的功能也受到影響。相對的,相同劑量的葡萄糖皮質素卻沒有造成蝕骨細胞的粒線體功能顯著的改變,氧化壓力也沒有上升,反而呈現下降趨勢。如此相反的現象,可能可以藉由一氧化氮合酶nos2基因表現量來說明,在蝕骨細胞中一氧化氮合酶表現是被抑制的,在成骨細胞中則是上升的。除了氧化壓力的探討,我們也繼續探討葡萄糖皮質素對粒線體的影響與氧化壓力的關係,實驗結果呈現,由葡萄糖皮質素所引起的質子洩漏與非粒線體的呼吸作用可能是造成細胞氧化壓力上升的主因。並且長時間的葡萄糖皮質素刺激,累積了上述的細胞變化,導致粒線體崩解和cytochrome C釋放,進而導致成骨細胞的凋亡。延續這樣的觀點,我們繼續的研究葡萄糖皮質素如何調控粒線體的功能。葡萄糖皮質素的受器在與葡萄糖皮質素結合後,會進入細胞核中調控基因的表現。所以從粒線體的型態以及粒線體調控基因的表現做探討,發現短時間的葡萄糖皮質素刺激,會促進粒線體生成,但是隨後粒線體開始分裂成較小的型態,然後細胞開始走向凋亡。綜合整個研究,從葡萄糖皮質素刺激成骨細胞後, 造成氧化壓力的上升,引起質子洩漏,同時調控粒線體基因促使粒線體分裂,最終導致成骨細胞凋亡,實驗結果前後呼應。藉此研究了解,需要使用高劑量或長期使用葡萄糖皮質素的患者治療計畫很重要的一環,調整輔助治療以減少氧化壓力來降低骨鬆之副作用。 | zh_TW |
dc.description.abstract | Glucocorticoid-induced bone loss is the most common form of secondary osteoporosis and the important cause of osteoporosis in the young adults. Among the different types of bone cells, high dose of exogenous glucocorticoids triggers apoptosis in the osteocytes and osteoblasts. Previous literature suggest that death of osteoblasts and osteocytes are associated with oxidative stress, although the mechanisms are not fully understood. Also, it is not clear whether glucocorticoids generate oxidative stress to osteoclasts. First part of this study, we demonstrated the effects of exogenous glucocorticoids on osteoblastic mitochondrial functions and elevated intracellular oxidative stress in a dose- and time-dependent manner. In contrast, the same dose of glucocorticoids did not induce mitochondria dysfunctions and oxidative stress in osteoclasts. Also, the production of reactive oxygen/nitrogen species was decreased in osteoclasts. The opposite effects may be explained by the nitrogen oxide synthase-nos2 expression level which is suppressed in osteoclasts but elevated in osteoblasts. We further revealed that glucocorticoids affect mitochondrial functions. The glucocorticoids induced increase of proton leak and non-mitochondria respiration suggest a potential source of glucocorticoids induced oxidative stress. Long term incubation of glucocorticoids accumulates these detrimental changes and result in cytochrome C release and mitochondria breakdown, consequently, lead to apoptosis in osteoblasts. In this regard, we also visualized the morphological alterations of mitochondria by staining with mitotracker and detect gene expression of mitochondrial biogenesis, resulting that mitochondrial biogenesis were transiently upregulated after treated with dexamethasone (DEX). But mitochondria fission also increased, and apoptosis became prominent. Our results indicated that the primary effects of glucocorticoids on mitochondria is promoting their functions and biogenesis. Mitochondria breakdown and the activation of the apoptotic pathways appeared to be the secondary effect after long term treatment. In our study, we know that we have to make an adjuvant therapy strategy for long-term or high dose steroid demanded patients to prevent bone loss. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T07:13:41Z (GMT). No. of bitstreams: 1 ntu-108-D97642005-1.pdf: 5309936 bytes, checksum: 781c6c2afadfb0853e4e1eda8173bb79 (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 口試委員會審定書…………..………………………………………… i
誌謝………………………………………………………………….… ii 中文摘要……………………………………………………………… iii Abstract………………………………..……………………….……... iv Chapter I: Exogenous glucocorticoid-induced osteoporosis: A literature reviews Background………………………… ………………….……..…. 1 Glucocorticoids – Clinical use, Side Effects, and Risks……......... 1 Glucocorticoid-Induced Osteoporosis…….……..……….………. 2 Glucocorticoids increase production of reactive oxygen species in cell…………………………..……..….……….……… 4 Glucocorticoids affect the mitochondria possibly through several different routes.……………..………………..……..……. 4 Chapter II: Different Susceptibilities Of Osteoclasts And Osteoblasts To Glucocorticoid-Induced Oxidative Stress And Mitochondrial Alterations……………….….…...…..…….. 6 Abstract……………………………………...………...….……… 6 Introduction…..……………………..………….….……...……… 8 Materials and Methods…..…………..…………..………..……… 11 Results……………………………………………………….…… 16 Discussion……………………………..…………………….…… 22 Figures II…………………………………………………….…… 29 Figure II-1. Effects of DEX on the proliferation of osteoblasts and osteoclasts…………..….…........ 29 Figure II-2. Measurement of DEX induced oxidative stress in osteoblasts and osteoclasts…..…..….... 30 Figure II-3. Effects of DEX on the antioxidant gene expression of osteoblasts and osteoclasts…....… 31 Figure II-4. Effects of DEX on the iNOS gene expression of osteoblasts and osteoclasts……..……….…… 32 Figure II-5. The mitochondrial function was altered in osteoblasts treated with DEX..……………...….. 33 Figure II-6. Detection of cytochrome C release in osteoblasts and osteoclasts by western blot analysis…......… 34 Chapter III: Glucocorticoids transiently upregulates mitochondrial biogenesis in osteoblasts…………………..………..….. 35 Abstract…………….……….…….…..……………………..…… 36 Introduction……….………………………………………..…….. 37 Materials and Methods…..…………………………………..…… 39 Results………….………..………………………………..……… 43 Discussion…….………………………………….……….……… 47 Figure III…………………...……………………..……………… 51 Figure III-1. Mitochondrial genes upregulated shortly after DEX treatment in osteoblasts…………..………. 51 Figure III-2. Mitochondria biogenesis mediated genes transiently upregulated in osteoblasts after DEX treatment……………………………….… 52 Figure III-3. The density of mitochondria increased in osteoblasts after DEX treatment……………...... 53 Figure III-4. Delayed appearance of mitochondrial fusion genes in osteoblasts after DEX treatment……... 54 Figure III-5. Mitochondrial fission genes upregulated in osteoblasts after long-term incubation with DEX………………………………………….… 55 Conclusion……………………………………………….……….……. 56 Abbreviations………………………………………………..………… 57 References…….………………………………………………….……. 59 | |
dc.language.iso | en | |
dc.title | 外源性葡萄糖皮質素誘發骨鬆之細胞與分子機轉 | zh_TW |
dc.title | Cellular and molecular mechanism of exogenous glucocorticoid-induced osteoporosis | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 劉江川(JIANG-CHUAN LIU),蕭勝文(SHENG-WEN SHAW),彭邵于(SHAU-YU PENG),林群書(CHUN-SHU LIN),沈培弘(Pei-Hung Shen) | |
dc.subject.keyword | 外源性葡萄糖皮質素,骨鬆, | zh_TW |
dc.subject.keyword | exogenous glucocorticoid,osteoporosis, | en |
dc.relation.page | 72 | |
dc.identifier.doi | 10.6342/NTU201901508 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-07-17 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 生物科技研究所 | zh_TW |
顯示於系所單位: | 生物科技研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-108-1.pdf 目前未授權公開取用 | 5.19 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。