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研究生:許君兆
研究生(外文):Hsu Chun-Chao
論文名稱:透過RANKL,多脂糖和雌激素來研究一氧化氮的訊息在破骨細胞中的作用
論文名稱(外文):A study of NO signaling in osteoclasts through RANKL, LPS and estrogen
指導教授:徐佳福史中
學位類別:碩士
校院名稱:國防醫學院
系所名稱:生物及解剖學研究所
學門:生命科學學門
學類:生物訊息學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:89
中文關鍵詞:雌激素
外文關鍵詞:RANKL
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一氧化氮是一種在生理上扮演多功能角色的氣體分子,近年來的研究指出,除了當作神經傳導分子、使血管平滑肌放鬆、使血小板聚集和調控免疫系統之外,一氧化氮在骨細胞的生理功能上也扮演著很重要的角色。在許多臨床研究指出,發炎反應會使得破骨細胞聚集,導致骨質的流失,在其他的研究中,學者指出雌激素在發炎反應中是透過抑制誘發型的一氧化氮合成酶與其他物質來達到抑制發炎的效果。但是大多數的研究都著重在雌激素如何透過造骨細胞來影響破骨細胞。所以我的實驗目的想要研究的是透過RANKL、脂多糖(LPS)以及雌激素來研究一氧化氮這個訊息分子在破骨細胞中所扮演的角色。在一氧化氮螢光系統中,我使用了NOR-3這個廣泛的被拿來研究一氧化氮對細胞生理功能有什麼影響的一氧化氮供給者。藉著NOR-3我證明了此系統的確是可以拿來偵測破骨細胞內一氧化氮即時的增減。但是我卻沒有看到在研究報告指出的RANKL和ionomycin也可使一氧化氮的量增加的情況。而另一方面我使用了RAW 264.7這個老鼠的單核球細胞株來研究在破骨細胞前驅細胞與成熟的破骨細胞中一氧化氮的角色是否有所不同。在RAW 264.7細胞中,不管是LPS(200 ng/ml)或RANKL(16 ng/ml)均可以促使iNOS在mRNA以及蛋白質量增加,但是在初級培養的破骨細胞則無。而在免疫螢光的部份,在兩種細胞中以LPS、RANKL刺激以後,的確可以觀察到在控制組所沒有的iNOS明顯在細胞表現。而在RAW 264.7細胞中藉著測量硝酸根以及亞硝酸根來達到測量一氧化氮產物的實驗中,除了加入LPS的組別明顯的使一氧化氮增加之外,其他組別與control組差異不大。結論:由DAF-FM DA建立的一氧化氮螢光系統可以偵測破骨細胞內一氧化氮即時的增減。RANKL與LPS對於破骨細胞的前驅細胞和成熟的破骨細胞所產生的作用不一樣。在前驅細胞中,LPS與RANKL可以在mRNA level誘導出iNOS,蛋白質量也可,但是兩者的效果有所差距。而此種情況不會受到雌性素明顯的抑制。
Nitric oxide is a gas molecular which have pleiotropic role in physiology. Recently studies indicated nitric oxide also play an important role in bone cell function. Several clinical studies have shown that bone loss may be attributed to osteoclast recruitment induced by mediators of inflammation. In different experimental paradigms investigators have demonstrated that estrogen exhibits antiinflammatory activity by preventing the induction of iNOS and other components of the inflammatory reaction. However, most investigators studied how estrogen to effect osteoclast by regulating osteoblast. The purpose of this study was to study of NO signaling in osteoclasts through RANKL, LPS and estrogen. Nitric Oxide fluorescence system in purified rabbit mature osteoclasts was established by using a Ntric oxide fluorescence indicator, DAF-FM DA. Result showed that cell permeable nitric oxide donor, NOR-3, increased fluorescent intensity in 8.3 μM DAF-FM labeled osteoclasts. We also used RANKL and Ionomycin which were known to increase NO production in osteoclast. But they could not increase DAF-FM fluorescent intensity as NOR-3. RAW 264.7 cell general use to study osteoclast and can be induced to osteoclast-like cell by stimulating RANKL. We successfully detected iNOS mRNA and protein expression in RAW 264.7 cell after LPS (200 ng/ml) or RANKL (16 ng/ml) stimulation for seven days. And the result of immunofluoresnce labeling indicated that seems not all RAW 264.7 cell could be induced iNOS. These results indicated that RAW 264.7 cell can use to study iNOS in osteoclast. We also measured nitric oxide products, including nitrate and nitrite and found only LPS could induce NO production increase.
頁次
英文摘要 Ⅵ
中文摘要 Ⅶ
第一章 緒言 1
第一節 研究背景 1
第二節 腫瘤壞死因子 6
壹、腫瘤壞死因子群 6
貳、腫瘤壞死因子受體群 7
第三節 RANKL與其受體 9
壹、OPG 9
貳、RANKL 10
參、RANK 11
肆、OPG對骨組織的作用 12
伍、RANKL對骨組織的作用 13
陸、RANK對骨組織的作用 13
第四節 RANK在細胞內訊息傳遞 15
壹、 TRAF 15
貳、 JNK 17
參、 NF-B 19
第五節 雌激素 20
壹、雌激素的生物特性與作用 20
貳、雌激素與停經後骨質疏鬆症 22
參、雌激素接受器………………………………………………..23
第六節 1,25-dihydroxyvitamine D3 25
第七節 破骨細胞 27
壹、骨骼之構造 27
貳、破骨細胞 28
參、骨再塑作用 29
肆、骨再塑的過程 30
第八節 一氧化氮…………………………………………………..33
壹、 簡述一氧化氮與骨骼之連………………………………...33
貳、 ㄧ氧化氮的合成及控……………………………………...34
参、一氧化氮合成酶在骨頭中的表現…………………………..36
肆、一氧化氮對骨再吸收(bone resorption)的影響…………..37 第九節 脂多糖……………………………………………………39
第十節 研究的動機與目的 41 第二章 材料與方法 42
第一節 實驗材料 42
壹、培養液與化學試劑 42
第二節 實驗方法 45
壹、破骨細胞的取得 45
貳、蛋白質標準曲線的建立及破骨細胞蛋白質濃度定量 46
參、免疫沈澱法 46
肆、硫酸十二酯鈉聚丙烯銨膠體電泳法 46
伍、西方點漬法 47
陸、一氧化氮螢光染色………………………………………….48
柒、萃取RNA………………………………………………… …48
捌、逆轉錄聚合酶鏈鎖反應……………………………………..49
玖、RAW 264.7小鼠單核球細胞株培養………………………..50
拾、免疫螢光染色………………………………………………...50
拾壹、Nitrate colorimetric assay…………………………………..51
第三章 結果 52
第四章 討論………………………………………………………….72
第五章 結論 73
參考文獻 74
1.Aloyzm, R. S., Bamji, S. X., Pozniak, C. D., Toma, J. G., Atwal, J., Kuplan, D. R., Miller, F. D. P53 is essential for developmental neuron death as regulated by the Trk and p75 neurotrophin receptors. J. Cell. Biol. 143: 1691-1703, 1998.

2.Anderson, D. M., Maraskovsky, E., Billingsley, W. L., Dougall, W. C., Tometsko, M. E., roux, E. R., Teepe, M. C., DuBose, R. F., Cosman, D., and Galibert, L. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390: 175-9, 1997.

3.Androlewicz, M. J., Browning, J. L., and Ware, C. F. Lymphotoxin is expressed as a heteromeric complex with a distinct 33-kDa glycoprotein on the surface of an activated human T cell hybridoma. J. Biol. Chem. 267: 2542-2547, 1992.

4.Arch, R. H., and Thompson, C. B. 4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB. Mol. Cell Biol. 18: 558-565, 1998.

5.Ashkenazi, A., and Dixit, V. M. Death receptors: signaling and modulation. Science 281: 1305-1308, 1998.

6.Baeuerle, P. A., and Baltimore, D. NF-kB: Ten Years After. Cell 87: 13-20.1996.

7.Bagrodia, S., Derijard, B., Davis, R. J., and Cerione, R. A. Cdc42 and PAK-mediated signaling leads to Jun kinase and p38 mitogen-activated protein kinase activation. J Biol Chem 270: 27995-27998, 1995.

8.Baldwin, A. S. The NF-kB and I-kB proteins: new discoveries and insights. Annu. Rev. immunol. 14: 639-681, 1996.

9.Baron R, Neff L, Roy C, Boisvent A and Caplan M. Evidence for a high and specific concentration of Na,K -ATPase in the plasma membrane of the osteoclast. Cell 46: 311-320, 1986.

10.Beutler, B., and van Huffel, C. Unraveling function in the TNF ligand and receptor families. Science 264: 667-8, 1994.

11.Blank, J. L., Gerwins, P., Elliott, E. M., Sather, S., and Johnson, G. L. Molecular cloning of mitogen-activated protein/ERK kinase kinase (MEKK)2 and 3. Regulation of sequential phosphorylation pathways involvingmitogen-activated protein kinase and c-Jun kinase. J Biol Chem 271: 5361-5368, 1996.

12.Boyle, W. J., Kung, Y., Lacey, D. L., Sarosi, I., Dunstan, C. R., Timms, E., Tan, H.-L., Elliott, G., Kelley, M. J., Colombero, A., Elliott, R., Scully, S., Capparelli, C., Morony, S., and Penninger, J. Osteoprotegerin ligand (OPGL) is required for murine osteoclastogenesis. J.Bone Miner. Res. 23, S189 (Abstract), 1998.

13.Brian R. Wong, Regis Josien, Soo Young Lee, Masha Vologodskaia, Ralph M. Steinman, and Yongwon Choi. The TRAF family of signal transducers mediates NF-B activation by the TRANCE receptor. The Journal of Biological Chemistry 273: 28355-28359, 1998.

14.Brommage R and DeLuca HF. Evidence that 1,25-dihydroxyvitamine D3 is the physiologically active metabolite of vitamine D3. Endocrine reviews 6: 491-511, 1985.

15.Broner, F. Calcium and osteoporosis. Am. J. Clin. Nutr. 60: 831-839, 1994.

16.Brown, J. L., Stowers, L., Bear, M., Trejo, J., Coughlin, S., and chant, J. Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathways. Curr Biol 6: 598-605, 1996.

17.Bryant G. Darany, Jian Nis, Paul a. Moore, and Bharat B. Aggarwal. Activation of NF-B by RANK Requires Tumor necrosis factor receptor-associated Factor (TRAF)6 and NF-B-inducing kinase. The Journal of Biological Chemistry 274: 7724-7731, 1999.

18.Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H. L., Lacey, D. L., Boyle, W. J., and Simonet, W. S. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12: 1260-1268, 1998.

19.Burger EH, Meer JWM, Gever JS, Gribnau JC, Thesingh CW and Furth R. In vitro formation of osteoclasts form long-term cultures of bone marrow mononuclear phagocytes. J. Exp. Med. 156: 1604-1614, 1982.

20.Burr DB and Martin RB. Errors in bone remodeling : Toward a unified theory og metabolic disease. Am. J. Anat. 186: 186-216, 1989.


21.Cao, Z., Xiong, J., Takeuchi, M., Kurama, T., and Goeddel, D. V. TRAF6 is a signal transducer for interleukin-1. Nature 383: 443-446, 1996.

22.Chen, Y. R., Tan, T. H. Lack of correlation in JNK activation and p53-dependent Fas expression induced by apoptotic stimuli. Biochem. Biophys. Res. Comm.256: 595-599, 1999.

23.Cheng, G., A. M. Cleary, Z.-S. Ye, D. I. Hong, S. Lederman, and D. Baltimore. Involvement of CRAF1, a relative of TRAF, in CD40 signaling. Science 267: 1494-1498, 1995.

24.Christako S., S.R.Gill, S.Lee, and H.Li. Molecular aspects of calbindins. J. Nutrition 122: 678-682, 1992.

25.Compston JE. Osteoporosis. Clin. Endocrinol. 33: 653-682, 1990.

26.Corvol MT, Du Bois MB, Garabedian M, Pezant E, and Balsan S. Vitamin D and cartilage.I. In vitro metabolism of 25-hydroxycholecalciferol by cartilage. Endocrinology 102: 1262-1268, 1978.

27.Coso, O. A., Chiariello, M., Yu, J.C., Teramoto, H., Crespo, P., Xu, N., Miki, T., and Gutkind, J. S. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathways. Cell 81: 1137-1146, 1995.

28.Dadgostar H, Cheng G. An intact zinc finger is required for tumor necrosis factor receptor-associated factor-mediated nuclear factor-B activation but is dispensible for c-Jun N-terminal kinase signaling. J Biol Chem. 273: 24775-24780, 1998.

29.Darnay, B. G., Haridas, V., Ni, J., Moore, P. A., and Aggarwal, B. B. Characterization of the intracellular domain of receptor activator of NF-B(RANK). Interaction with tumor necrosis factor receptor-associated factors and activation of NF-B and c-Jun N-terminal kinase. J. Biol. Chem. 273: 20551-20555, 1998.

30.DeLuca, H.F. The vitamin D story: a collaborative effect of basic science and clinical medicine. FASEB J. 2: 224-236, 1988.

31.Demay M.B., J.M. Gerardi, H.F. DeLuca, and H. M Kronenberg. DNA sequences in the rat osteocalcin gene that bind the 1,25-dihydroxyvitamine D3 receptor and confer responsiveness to 1,25-dihydroxyvitamine D3. Proc. Natl. Acad. Sci. USA. 87: 369-373, 1990.

32.Derijard, B., Raingeaud, J., Barrett, T., Wu, I. H., Han, J., Ulevitch, R. J., Davis RJ. Independent human MAP kinase signal transduction pathways defined by MEK and MKK isoforms. Science 267: 682-685, 1995.

33.Domon T and Wakita M. The three-dimensional structure of the clear zone of a cultured osteoclast. J. Electron Microsc. 40: 34-40, 1991.

34.Dong, C., Yang, D. D., Wysk, M., Whitmarsh, A. J., Davis, R. J., Flavell, R. A. Defective T Cell Differentiation in the Absence of Jnk1. Science 282: 2092-2095, 1998.

35.Eriksen EF, Colvard DS, Berg NJ. Et al. Evidence of estrogen receptors in normal human osteoblast-like cells. Science 241: 84, 1988.

36.Eriksen EF and Kassem M. The cellular basis of bone remodeling. Triangle. 31: 45-57, 1992.

37.Eriksen EF, Melsen F and mesekilde L. Reconstruction of the resorptive site in iliac trabecular bone : A kinetic model for bone resorption. Metab. Bone Dis. Rel. Res. 5: 235-242, 1984.

38.Felson, D.T., Zhang, Y., Hannan,M.T., Kiel, D.P., and Wilson, P.W.F. The effect of postmenopausal estrogen therphy on bone density in elderly women. N. Engl. J. Med. 329: 1141-1146, 1993.

39.Franzoso, G., Carlson, L., Xing, L., Poljak, L., Shores, E. W., Brown, K. D., Leonardi, A., Tran, T., Boyce, B. F. & Siebenlist, U. Requirement for NF-kappaB in osteoclast and B-cell development. Genes Dev. 11: 3482-3496, 1997.

40.Fraser DR and E. Kodicek. Unique biosynthesis by kidney of a biologically active vitamin D metabolite. Nature 228: 764-766, 1970.

41.Frost HM. Bone remodeling dynamics. Thomas CC, Springfield, USA, 1963.

42.Galcheva-Gargova, Z., Derijard, B., Wu, I. H., Davis R. J. An osmosensing signal transduction pathway in mammalian cells. Science 265: 806-808, 1994.

43.Galibert L, Tometsko ME, Anderson DM, Cosman D, Douggall WC. The involvement of multiple tumor necrosis factor receptor (TNFR)-associated of NF-B, a member of the TNFR superfamily. J Biol Chem. 273: 34120-34127, 1998.

44.Gallagher, J.C. and goldgar, D. Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol. Annals of Internal Medical 113: 649-655, 1990.

45.Ganong, W.F. Hormonal control of calcium metabolism and the physiology of bone. Medical Physiology 21: 413-426, 1991.

46.Gearing, M., Rebeck, G. W., Hyman, B. T., Tigges, J., and Mirra, S. S. . Neuropathology and apolipoprotein E profile of aged chimpanzees; implications for Alzheimer disease. Proc. Natl. Acad. Aci. USA. 91: 9382-9386, 1994.

47.Geidel H. Therapic der osteoporosis. Z. Arzyl Fortbild (Jena). 89( 1 ): 13-20, 1995 Feb.

48.Geng, Y., Valbracht, J., and Lotz, M. Selective activation of the mitogen-activated protein kinase subgroups c-Jun NH2 terminal kinase and p38 by IL-1 and TNF in human articular chondrocytes. J Clin Invest 98: 2425-2430, 1996.

49.Gruss, H. J., and Dower, S. K. Tumor necrosis factor ligand superfamily: involvement in the pathology of malignant lymphomas. Blood 85: 3378-404, 1995.

50.Gupta, S., Campbell, D., Derijard, B., Davis R. J. Transcription factor ATF regulation by the JNK signal transduction. Science 267: 389-393, 1995.

51.Haussler MR et al. Molecular biology of the vitamin D hormone. Recent Progress In Hormone Research 44 : 263-305, 1988.

52.Henery HL and Norman AW . Vitamin D : two dihydroxylated metabolites are required for normal chicken egg hatchability. Science 201: 835-837, 1978.

53.Hibi, M. Lin, A., Smeal, T., Minden, A., karin, M. Identification of an oncoprotein and UV-resposive protein kinase that binds and potentiates the c-Jun activation domain. Genes. & Dev. 7: 2135-2148, 1993.

54.Hofbauer LC, Lacey DL, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S. Interleukin-1 and tumor necrosis factor-, but not interleukin-6 stimulate osteoprotegerin ligand gene expression in human osteoblastic cells. Bone.24: in press, 1999.

55.Hsu, H., Lacey, D. L., Dunstan, C. R., Solovyev, I., Colombero, A., Timms, E., Tan, H. L., Elliott, G., Kelley, M. J., Sarosi, I., et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc. Natl. Acad. Sci. USA 96: 3540-3545, 1999.

56.Hu, H. M., K. O’Rourke, M. S. Boguski, and V. M. Dixit. A novel RING finger protein interacts with the cytoplasmic domain of CD40. J. Biol. Chem. 269: 30069-30072, 1994.

57.Hui S.L., Slemenda C.W., Johnston C.C.Jr. Age and bone mass as predictors of fracture in a prospective study. J Clin Invest 1, 81: 1804-1809, 1988.

58.Iotsova, V., Caamano, J., Loy, J., Yang, Y., Lewin, A., and Bravo, R. Osteopetrosis in mice lacking NF-kappa B1 and NF-kappa B2. Nat. Med. 3: 1285-1289, 1997.

59.Ishida, T., T. Tojo, T. Aoki, N. Kobayashi, T. Ohishi, T. Watanabe, T. Yamamoto, and J.-I. Inoue. TRAF5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling. Proc. Natl. Acad. Sci. 93: 9437-9442, 1996a.

60.Ishida, T., Mizushima, S., Azuma, S., Kobayshi, N., Tojo, T., Suzuki, K., Aizawa, S., Watanabe, T., Mosialos, G., Kieff, E., Yamamoto, T., and Inoue, J. Identification of TRAF6, a novel tumor necrosis factor receptor-associated factor protein that mediates signalung from an amino terminal domain of the CD40 crytoplasmic region. J. Biol. Chem. 271: 28745-28748, 1996b.

61.Itoh, N., Yonehara, S., Ishii, A., Yonehara, M., Mizushima, S., Sameshima, M., Hase, A., Seto, y., and Nagata, S. The polypeptide encoded by the cDNA for human cell surface antigan Fas can mediate apoptosis. Cell 66: 233-43, 1991.

62.Kanis, J.A. Calcium nutrition and its implications for osteoporosis. Part I. Children and healthy adults. Europ. J. Clin. Nutr.48: 757-767, 1994.

63.Kanis, J.A. Calcium nutrition and its implications for osteoporosis. Part II. After menopause. Europ. J. Clin. Nutr. 48: 833-841, 1994.

64.Kong, Y. Y., U. Feige, I. Sarosi, B. Bolon, A. Tafuri, S. Morony, C. Capparelli, J. Li, R. Elliott, S. McCabe, T. Wong, G. Campagnuolo, E. Moran, E. R. Bogoch, G. Van, L. T. Nguyen, P. S. Ohashi, D. L. Lacey, E. Fish, W. J. Boyle, and J. M. Penninger. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402: 304, 1999.


65.Kuan, C. Y., Yang, D. D., Samanta, Roy, D. R., davis, R. J., rakic, P., Flavell, R. A. The Jnk1 and Jnk2 Protein Kinase Are required for regional specific apoptosis during early brain development. Neuron 22: 667-676, 1999.

66.Kushida K. Pharmacologic therapy of osteoporosis. Nippon Rinsho 52(9): 2367-2377.

67.Kwon BS, Wang S, Udagawa N, Haridas V, Lee Zh, Kim KK, Oh K-O, Green J, Li Y, Su J, Gentz r, Aggarwal BB, Ni J. TR1, a new member of the tumor necrosis factor receptor family, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption. FASEB J 12: 845-854, 1998.

68.Kyrakis, J. M., Banerjee, P., Nikolakaki, E., Dai, T., Rubie, E. A., Ahmad, M. F., Avruch, J., Woodgett, J. R. The stress activated protein kinase subfamily of c-Jun kinase. Nature 369: 156-160, 1994.

69.Lacey, D. L., Timms, E., Tan, H. L., Keley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., Hsu, Sullivan, J., Hawkins, N., Davy, E., Capparelli, C., Eli, A., Qian, Y. X., Kaufman, S., Sarosi, I., Schlhoub, V., Senaldi, G., Guo, J., Delaney, J., and Boyle, W. J. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93: 165-76, 1998.

70.Liu, Z.-G., Hsu, H., Goeddel, D. V., and Karin, M. Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kappaB activation prevents cell death. Cell 87: 565-576, 1996.

71.Lomaga, M. A., Yeh, W. C., Sarosi, I., Duncan, G. S., Furlonger, C., Ho, A., Morony, S., Capparelli, C., Van, G., Kaufman, S., et al. TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev. 13: 1015-1024, 1999.

72.Lorenz C. H., Sundeep K., Colin R. D., David L. L., William J. B., and B. Lawrence Riggs. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res.15: 2-12, 2000.

73.Macintyre I, Imogen M., Evans I.M.A. Larkins R.G. Vitamin D Clinical Endocrinology 6: 65-79, 1977.

74.Mackay, I. P. and M. Crossley. Zinc fingers are sticking together. Trends Biochem. Sci.23: 1-4, 1998.

75.Malinin, N. L., Boldin, M. P., Kovalenko, A. V., and Wallach, D. MAP3K-related kinase involved in NF-B induction by TNF, CD95 and IL-1. Nature 385: 540-544, 1997.

76.Matsuda, S., Moriguchi, T., Koyasu, S., Nishida, E. T lymphocytes activation signals for interleukin-2 production of MKK6-p38 and MKK7-JNK/SAPK signaling pathways sensitive to cyclospoein. A. J. Biol. Chem. 273: 123778-123782, 1998.

77.Matsui, K., Fine, A., Zhu, B., marshak-Rothstein, A., Ju, S. T. Identification of two NF-kB sites in mouse CD95 ligand (Fas ligand) promoter: functional analysis in T cell Hybridoma. J. Immunol. 161: 3469-3473, 1998.

78.Maundrell, K., Antossan, B., Magnenat, E., Camps, M., Muda, M., chabert, C., Gilleiron, C., Boschert, U., Vial-Knecht, E., Martinou, J. C., Arkinstallm, S. Bcl-2 Undergoes Phosphorylation by c-Jun N-terminal Kinase/Stress-activated Protein Kinase in the presence of the ponstitutively active GTP-binding protein Rac1. J. Biol. Chem. 272: 25238-25242, 1997.

79.May, M. J., and Ghosh, S. Signal transduction through NH-kappa B. Immunol. Today 19; 80-88, 1998.

80.Milne, D. M., Campbell, L. E., Campbell, D. G., Meek, D. E. p53 is phosphorylated in vitro by an ultraviolet radiation-induced protein kinase characteristic of the c-Jun kinase, JNK1. J. Biol. Chem. 270: 5511-5518, 1995.

81.Minden, A., Lin, A., Claret, F. X., Abo, A., and Karin, M. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell 81: 1147-1157, 1995.

82.Mizuno, A., Amizuka, N., Irie, K., Murakami, A., Fujise, N., Kanno, T., Sato, Y., Yano, K., Shima, N., Washida, N., Tsuda, E., Morinaga, T., Higashio, K., and Ozawa, H. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem. Biophys. Res. Commun. 247: 610-615, 1998.

83.Mosialos, G., M. Birkenbach, R. Yalamanchili, T. vanArsdale, C. Ware, and E. Kieff. The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell 80: 389-399, 1995.

84.Muzio, M., Ni, J., Feng, P., and Dixit, V. M. IRAK(Pelle) family member TRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science 278: 1612-1615, 1997.

85.Nagata, S. Apoptosis by death factor. Cell 88: 355-65, 1997.

86.Nakano, H., H. Oshima, W. Chung, L. Williams-Abbott, C. F. Ware, H. Yagita, and K. Okumura. TRAF5, an activator of NF-B and putative signal transducer for the lymphotoxin-receptor. J. Biol. Chem. 271: 14661-14664, 1996.

87.Natoli, G.,Costanzo, A., Moretti, F., Fulco, M. balsano, C., Levrero, M. Tumor necrosis factor (TNF) receptor 1 signaling downstream of TNF receptor associated factor 2. Nuclear factor kappaB (NF kappaB)-inducing kinase requirement for activation of activating protein 1 and NF kappaB but not of c-Jun N-terminal kinase/stress activated protein kinase. J. Biol. Chem. 272: 26079-26082, 1997.

88.Norman AW et al. 1,25(OH)2-vitamine D3, a steroid hormone the produces biological effect via both genomic and non-genomic pathway. J. steroid Biochemistry & Molecular Biology 41: 231-240, 1992.

89.Pan, G., O’Rourke, K., Chinnaiyan, a. M., Gentz, R., Ebner, R., Ni, J., and Dixit, V. M. The receptor for the cytotoxic ligand TRAIL. Science 276: 111-3, 1997.

90.Pols HAP, Birkenhager JC, Foeken JA et al. Vitamin D : a modulator of cell proliferation and differentiation. J. Steroid Biochemistry & Molecular Biology 37 : 873-876, 1990.

91.Reginster J.Y. Calcitonin foe prevention and treatment of osteoporosis. Horm. Res, 9 5( 5A ): 44S-47S, 1993.

92.Reginster J.Y. Treatment of bone in elderly subjects : calcium, vitamin D, fluor, bisphosphonates, calcitonin. Hom Res 43(1-3): 83-88, 1995.

93.Regnier, C. H., C. Tomasetto, C. Moog-Lutz, M.-P. Chenard, C. Wendling, P. Basset, and M.-C. Rio. Presence of a new conserved domain in CART1, a novel member of the tumor necrosis factor receptor-associated protein family, which is expressed in breast carcinoma. J. Biol. Chem. 270: 25715-25721, 1995.

94.Reichel H, Koeffler HP and Norman AW. The role of vitamin D endocrine system in health and disease. New England J. Medicine 320: 980-991, 1989.

95.Riggs B.L., Gallagher J.C., Deluca H.F., Edis A.J., Lambert P.W., Arnaud C.D. A symdrome of osteoporosis, increased serum immunoreactive PTH, and inappropriately low serum 1,25-dihydroxy vitamin D. Mayo Clin Proc 53: 701-706, 1978.

96.Riggs BL, Melton LT, The world problem of osteoporosis insights afforded by epidiology. Bone 17 suppl: 505s-511s, 1995.

97.Rothe, M., S. C. Wong, W. J. Henzel, and D. V. Goddel. A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell 78: 681-692, 1994.

98.Roulston, A., Reinhard, C., amiri, p., and Williams, L. T. Early activation of c-Jun N-terminal kinase and p38 kinase regulate cell survival in response to tumor necrosis factor alpha. Journal of Biological Chemistry 273: 10232-10239, 1998.

99.Rubin CD. Southwestern internal medicine conference : Age-related osteoporosis. Am. J. Med. Sci. 301: 281-297, 1991.

100.Sabapathy, K., Hu, Y., Kalluki, T., Schreiber, M., David, J. P., Jochum, W., Wanger, E. F., Karin, M. JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development. Curr. Biol. 9: 116-125, 1999.

101.Sato, T., S. Irie, and J. C. Reed. A novel member of yhe TRAF family of putative signal transducing proteins binds to the cytosolic domain of CD40. FEBS Lett. 358: 113-118, 1995.

102.Sheridan, J. P., Marsters, S. A., Pitti, R. M., Gurney, A., Skubatch, M., Baldwin, D., Ramakrishnan, L., Gray, C. L., Baker, K., Wood, W. L., Goddard, A. D., Godwski, P., and Ashkenazi, A. Control of YTAIL-induced apoptosis by a family of signaling and decoy receptors [see comments]. Science 277: 818-21, 1997.

103.Simonet, W. S., Lacey, D. L., Dunstan, C. R., Helley, M., Chang, M.-S., Lüthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone,T., Shimamoto, G.,, DeRose, M., Elliott, R., Colombero, A., Tan, H.-L., Trail, G., Sullivan, J., Davy, E., Bucay, N., Renshaw-Gegg, L., Hughes, T. M., Hill, D., Pattison, W., Campbell, P., Sander, S., Van, G., Tarpley, J., Derby, P., Lee, R., and Boyle, W. J. Osteoprotegerin : a novel secreted protein involved in the regulation of bone density. Cell 89: 309-319, 1997.

104.Sindy C, Marks J and Steven NP. Bone cell biology : The of development, structure and function in the skeleton. Amer. J. Anat. 183: 1-44, 1988.

105.Smeal, T., Binetruy, B., Mercila, D., Grover-bardwuck, A., Heidecker, G., Rapp, U. R., Karin, M. Oncoprotein-mediated signaling cascade stimulates c-Jun acyivity by phosphorylation of Ser63 and 73. Mol. Cell. Biol.12: 3507-3513, 1992.

106.Song, H. Y., Regnier, C. H., Kirschning, C. J., Goeddel, D. V., and Rothe, M. Tumor necrosis factor(TNF)-mediated kinase cascades:Bifurcation of nuclear factor-B and c-jun N-terminal kinase(JNK/SAPK)pathways at TNF receptor-associated factor 2. Proc. Natl. Acad. Sci. U. S. A. 94: 9792-9726, 1997.

107.Tan H-L, Van G, Scully S, Shimamoto G, Kelley M, Boyle B, Dunstan C, Lacey D. Recombinant osteoprotegerin (OPG), a novel TNF-receptor family member, inhibits in vitro murine osteoclast formation from bone marrow precursors. (abstract P213). J Bone Miner Res 12(Suppl 1): S155, 1997.

108.Tanaka, M., Suda, T., haze, K., Nakamura, N., sato, K., Kimura, F., Motoyoshi, K., Mizuki, M., tagawa, S., Ohga, S., and Hatake, K. Drummond AH, Nagata S. fas ligand in human serum. Nat. Med. 2: 317-322, 1996.

109.Tartaglia, l. A., Ayres, T. M., Wong, G. H., and Goddel, D. V. A novel domain within the 55kd TNF receptor signals celll death. Cell 74: 845-53, 1993.

110.Tsuda E, Goto M, Mochizuki S-I, Yano K, Kobayashi F, Morinaga T, Higashio K. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Biochem Biophys Res Com 234: 137-142, 1997.

111.Tsukii N, Shima N, Mochizuki S, yamaguchi K, Kinosaki M, Yano K, Shibata O, Udagawa N, Yasuda H, Suda T, Higashio K. Osteoclast differentiation factor mediates an essential signal for bone resorption induced by 1,25-dihydroxyvitamin D3, prostaglandin E2, or parathyroid hormone in the microenvironment of bone. Biochem Biophys res Com 246: 337-341, 1998.

112.Veenstra TD et al. 1,25-dihydroxyvitamine D3 receptors in the central nervous system of the rat embro. Brain Research 804 : 193-205, 1998.

113.Wang, Z. Q., Ovitt, C., Grigoriadis, A. E., Mohle-Steinlein, U., ruther, U. & wagner, E. F. Nature (London) 360: 741-745, 1992.

114.Ware, C. F., vanArsdale, S., and VanArsdale, T. L. Apoptosis mediated by the TNF-related cytokine and receptor families. Journal of Cellular Biochemistry 60: 47-55, 1996.

115.Weiss L. Cell and Tissue Biology : A Textbook of Histology. Six edition, Urban & Schwarzenberg Inc., USA, 1988.

116.Wesche, H., Henzel, W. J., Shillinglaw, W., Li, S., and Cao, Z. MyD88: An adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7: 837-847, 1997.

117.Wiley, S. r., Schooley, k, Smolak, p. J., Din, W. S., huang, C. P., Nicholl, J. K., Sutherland, G. R., Smith, T. D., rauch, C., Smith, C. A., and et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3: 673-82, 1995.


118.Wong, B. R., Josien, R., Lee, S. Y., sauter, B., li, H. L., Steinman, R. M., and Choi, Y. TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. Journal of Experimental medicine 186: 2075-80, 1997.

119.Wong BR, Josien R, Young Lee S, Vologodskaia M, Steinman RM, Choi Y. The TRAF family of sihnal transducers mediates NF-kB activation by the TRANCE receptor. J Biol Chem. 273: 28355-28359, 1998.

120.Yamaguchi, K., Kinosaki, M., Goto, M., Kobayashi, F., Tsuda, E., Morinaga, T., and Higashio, K. Characterization of structural domains of human osteoclastogenesis inhibitory factor. J. Biol. Chem. 273: 5117-5123, 1998.

121.Yang, D. D., Conze, D., Whitmarsh, A. J., Barrett, T., Davis, R. J., Ricon, M., Flavell, R. A. Differentiation of CD4+ T Cells to Th1 Cells Requires MAP Kinase JNK2. Immunity 9: 575-585, 1998.

122.Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S-I, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci 95: 3597-3602, 1998.

123.Yeh, W. C., Shahinian, A., Speiser, D., Kraunus, J., Billia, F., Wakeham, A., de la Pompa, J. L., Ferrick, D., Hum, B., Iscove, N., et al. Early lethality, functional NF-B activation, and increased sensitivity to TNF-induced cell death in TRAF-2 deficient mice. Immunity 7: 715-725, 1997.

124.Yuasa, T., Ohno, S., Kehrl, J. H., and Kyriakis, J. M. Tumor necrosis factor signaling to stress-activated protein kinase(SAPK)/Jun NH2-terminal kinase(JNK) and p38. Germinal center kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38. J. Biol. Chem.273: 22681-22692, 1998.

125.Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524-526, 1987.

126.Moncada S, Higgs A. The L-arginine nitric oxide pathway. N Engl J Med 329:2002-2012, 1993.

127.Teitelbaum SL. Bone resorption by osteoclasts. Science 289:1504-1508, 2000.

128.MacDonald BR, Takahashi N, McManus LM et al. Formation of multinucleated cells that respond to osteotropic hormones in longterm human marrow cultures. Endocrinology 120:2326-2333, 1987.

129.Tsukii K, Shima N, Mochizuki S, Yamaguchi K, Kinosaki M, Yano K, Shibata O, Udagawa N, Yasuda H, Suda T, Higashio K. Osteoclast differentiation factor mediates an essential signal for bone resorption induced by 1 alpha,25-dihydroxyvitamin D3, prostaglandin E2, or parathyroid hormone in the microenvironment of bone. Biochem Biophys Res Comm 246:337-341, 1998.

130.Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165-176, 1998.

131.Lee SK, Lorenzo JA. Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology 140:3552-3561, 1999.

132.Roux S, Orcel P. Bone loss. Factors that regulate osteoclast differentiation: an update. Arthritis Res 2:451-456, 2000.

133.Feelisch M, Stamler JS. Methods in Nitric Oxide Research. Chichester: J. Wiley & Sons. 1996.

134.Malinski T, Taha Z. Nitric oxide release from a single cell measured in situ by a porphyrinic-based microsensor. Nature 358:676-678, 1992.

135.Bredt DS, Hwang PM, Glatt CE, Lowenstein C, Reed RR, Snyder SH. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature 351:714-718, 1991.

136.Robinson LJ, Weremowicz S, Morton CC, Michel T. Isolation and chromosomal localization of the human endothelial nitric oxide synthase (nos3) gene. Genomics 19:350-357, 1994.

137.Lowenstein CJ, Glatt CS, Bredt DS, Snyder SH. Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme. Proc Natl Acad Sci USA 89:6711-6715, 1992.

138.Michell BJ, Grif®ths JE, Mitchelhill KI, Rodriguez-Crespo I, Tiganis T, Bozinovski S, Ortiz de Montellano PR, Kemp BE, Pearson RB. The Akt kinase signals directly to endothelial nitric oxide synthase. Current Biol 9:845-848, 1999

139.Venema RC, Nishida K, Alexander RW, Harrison DG, Murphy TJ. Organisation of the bovine gene encoding the endothelial nitric oxide synthase. Biochimica Biophysica Acta 1218:413-420, 1993.

140.Uematsu M, Ohara Y, Navas JP, Nishida K, Murphy TJ, Alexander RW, Nerem RM, Harrison DG. Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am J Physiol 269:C1371-1378, 1995.

141.Hayashi T, Yamada K, Esaki T, Kuzuya M, Satake S, Ishikawa T, Hidaka H, Iguchi A. Estrogen increases endothelial nitric oxide by a receptor- mediated system. Biochem Biophys Res Comm 214:847-855,1995.

142.de Vera ME, Shapiro RA, Nussler AK, Mudgett JS, Simmons RL, Morris SM Jr, Billiar TR, Geller DA. Transcriptional regulation of human inducible nitric oxide synthase (NOS2) gene by cytokines: initial analysis of the human NOS2 promoter. Proc Natl Acad Sci USA 93:1054-1059, 1996.

143.Albina JE. On the expression of nitric oxide synthase by human macrophages. Why no NO? J Leukocyte Biol 58:643-649, 1995.

144.Sunyer T, Rothe L, Kirsch D, Jiang X, Anderson F, Osdoby P, Collin-Osdoby P. Ca2+ or phorbol ester but not in¯ammatory stimuli elevate inducible nitric oxide synthase messenger ribonucleic acid and nitric oxide (NO) release in avian osteoclasts: autocrine NO mediates Ca2+-inhibited bone resorption. Endocrinology 138:2148-2162, 1997.

145.Ralston SH, Todd D, Helfrich MH, Benjamin N, Grabowski PS. Human osteoblast-like cells produce nitric oxide and express inducible nitric oxide synthase. Endocrinology 135:330-306, 1994.

146.Nussler AK, DiSilvio M, Billiar TR, Hoffman RA, Geller DA, Selby R, Madrigas J, Simmons RL. Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin. J Exp Med 176:261-264, 1992.

147.Grabowski PS, MacPherson H, Ralston SH. Nitric oxide production in cells derived .from the human joint. Br J Rheum 35:207-212, 1996.

148.Ralston SH, Grabowski PS. Mechanisms of cytokine induced bone resorption: role of nitric oxide, cyclic guanosine monophosphate and prostaglandins. Bone 19:29-33, 1996.

149.Palmer RMJ. The L-arginine nitric oxide pathway. Curr Opin Nephrol Hyperten 2:122-128, 1993.

150.Brandi ML, Hukkanen M, Umeda T, Moradi-Bidhendi N, Bianchi S, Gross SS, Polak JM, MacIntyre I. Bidirectional regulation of osteoclast function by nitric oxide synthase isoforms. Proc Natl Acad Sci USA 92:2954-2958, 1995

151.Helfrich MH, Evans DE, Grabowski PS, Pollock JS, Ohshima H, Ralston SH. Expression of nitric oxide synthase isoforms in bone and bone cell cultures. J Bone Miner Res 12:1108-1115, 1997

152.MacPherson H, Noble BS, Ralston SH. Expression and functional role of nitric oxide synthase isoforms in human osteoblast-like cells. Bone 24:179-185, 1999

153.Fox SW, Chow JW. Nitric oxide synthase expression in bone cells. Bone 23:1±6, 1998

154.Hukkanen MV, Platts LA, Fernandez DMI, O'Shaughnessy M, MacIntyre I, Polak JM. Developmental regulation of nitric oxide synthase expression in rat skeletal bone. J Bone Miner Res 14:868-877,1999

155.Lowik CWGM, Nibbering PH, Van der Ruit M, Papapoulos SE. Inducible production of nitric oxide in osteoblast like cells and in fetal bone explants is associated with supression of osteoclastic bone resorption. J Clin Invest 93:1465-1472, 1994.

156.Ralston SH, Ho LP, Helfrich MH, Grabowski PS, Johnston PW, Benjamin N. Nitric oxide: a cytokine-induced regulator of bone resorption. J Bone Miner Res 10:1040-1049, 1995

157.van't Hof RJ, Ralston SH. Cytokine induced nitric oxide inhibits bone resorption by inducing apoptosis of osteoclast progenitors and suppressing osteoclast activity. J Bone Miner Res 12:1797-1804, 1997.

158.MacIntyre I, Zaidi M, Alam AS, Datta HK, Moonga BS, Lidbury PS, Hecker M, Vane JR. Osteoclastic inhibition: an action of nitric oxide not mediated by cyclic GMP. Proc Natl Acad Sci USA 88:2936-1940, 1991

159.van't Hof RJ, Ralston SH. Cytokine-induced nitric oxide inhibits bone resorption by inducing apoptosis of osteoclast progenitors and suppressing osteoclast activity. J Bone Miner Res 12: 1797-1804, 1997

160.Percival MD, Ouellet M, Campagnolo C, Claveau D, Li C. Inhibition of cathepsin K by nitric oxide donors: evidence for the formation of mixed disul®des and a sulfenic acid. Biochemistry 38:13574-13583, 1999

161.WEI ZOU and ZVI BAR-SHAVIT. Dual modulation of osteoclast differentiation by lipopolysaccharide. J Bone Miner Res 17:1211-1218, 2002

162. Jiang J, Li H, Fahid FS, Filbert E, Safavi KE, Spangberg LS, Zhu Q. Quantitative analysis of osteoclast-specific gene markers stimulated by lipopolysaccharide. J Endod. 32:742-746, 2006

163.Weitzmann, M. N. and R. Pacifici. Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest 116: 1186-94, 2006

164.林于櫻: 雌激素調節破骨細胞中RANK的表現及其所引起之訊息傳導途徑,國防醫學院生物及解剖學研究所碩士論文, 2001年

165.孫德宗: 雌性激素對兔子蝕骨細胞內RANK訊息傳遞之調控及影響, 國防醫學院生物及解剖學研究所碩士論文, 2003年

166.200蔡益堅,何彥瑤.1993年全國老年髖關節骨折之調查. 台灣省家庭計劃研究所老年研究叢刊. 1996;40
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