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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/45243完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 符文美(Wen-Mei Fu) | |
| dc.contributor.author | Tzu-Hung Lin | en |
| dc.contributor.author | 林子閎 | zh_TW |
| dc.date.accessioned | 2021-06-15T04:10:28Z | - |
| dc.date.available | 2012-03-12 | |
| dc.date.copyright | 2010-03-12 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-01-29 | |
| dc.identifier.citation | Akune T, Ohba S, Kamekura S, Yamaguchi M, Chung UI, Kubota N, Terauchi Y, Harada Y, Azuma Y, Nakamura K, Kadowaki T, Kawaguchi H. 2004. PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest 113(6):846-855.
Ali AA, Weinstein RS, Stewart SA, Parfitt AM, Manolagas SC, Jilka RL. 2005. Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation. Endocrinology 146(3):1226-1235. Almeida M, Han L, Martin-Millan M, Plotkin LI, Stewart SA, Roberson PK, Kousteni S, O'Brien CA, Bellido T, Parfitt AM, Weinstein RS, Jilka RL, Manolagas SC. 2007. Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids. J Biol Chem 282(37):27285-27297. Alvarez-Maqueda M, El Bekay R, Alba G, Monteseirin J, Chacon P, Vega A, Martin-Nieto J, Bedoya FJ, Pintado E, Sobrino F. 2004. 15-deoxy-delta 12,14-prostaglandin J2 induces heme oxygenase-1 gene expression in a reactive oxygen species-dependent manner in human lymphocytes. J Biol Chem 279(21):21929-21937. Arikawa T, Omura K, Morita I. 2004. Regulation of bone morphogenetic protein-2 expression by endogenous prostaglandin E2 in human mesenchymal stem cells. J Cell Physiol 200(3):400-406. Armour KE, Armour KJ, Gallagher ME, Godecke A, Helfrich MH, Reid DM, Ralston SH. 2001. Defective bone formation and anabolic response to exogenous estrogen in mice with targeted disruption of endothelial nitric oxide synthase. Endocrinology 142(2):760-766. Baeuerle PA, Henkel T. 1994. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol 12:141-179. Bakewell SJ, Nestor P, Prasad S, Tomasson MH, Dowland N, Mehrotra M, Scarborough R, Kanter J, Abe K, Phillips D, Weilbaecher KN. 2003. Platelet and osteoclast beta3 integrins are critical for bone metastasis. Proc Natl Acad Sci U S A 100(24):14205-14210. Bakker AD, Klein-Nulend J, Tanck E, Albers GH, Lips P, Burger EH. 2005. Additive effects of estrogen and mechanical stress on nitric oxide and prostaglandin E2 production by bone cells from osteoporotic donors. Osteoporos Int 16(8):983-989. Bondeson J, Browne KA, Brennan FM, Foxwell BM, Feldmann M. 1999. Selective regulation of cytokine induction by adenoviral gene transfer of IkappaBalpha into human macrophages: lipopolysaccharide-induced, but not zymosan-induced, proinflammatory cytokines are inhibited, but IL-10 is nuclear factor-kappaB independent. J Immunol 162(5):2939-2945. Bondeson J, Lauder S, Wainwright S, Amos N, Evans A, Hughes C, Feldmann M, Caterson B. 2007. Adenoviral gene transfer of the endogenous inhibitor IkappaBalpha into human osteoarthritis synovial fibroblasts demonstrates that several matrix metalloproteinases and aggrecanases are nuclear factor-kappaB-dependent. J Rheumatol 34(3):523-533. Boyle WJ, Simonet WS, Lacey DL. 2003. Osteoclast differentiation and activation. Nature 423(6937):337-342. Brennan FM, McInnes IB. 2008. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest 118(11):3537-3545. Burkhardt R, Kettner G, Bohm W, Schmidmeier M, Schlag R, Frisch B, Mallmann B, Eisenmenger W, Gilg T. 1987. Changes in trabecular bone, hematopoiesis and bone marrow vessels in aplastic anemia, primary osteoporosis, and old age: a comparative histomorphometric study. Bone 8(3):157-164. Callejas NA, Castrillo A, Bosca L, Martin-Sanz P. 1999. Inhibition of prostaglandin synthesis up-regulates cyclooxygenase-2 induced by lipopolysaccharide and peroxisomal proliferators. J Pharmacol Exp Ther 288(3):1235-1241. Carmeliet P. 2002. Integrin indecision. Nat Med 8(1):14-16. Chae HJ, Chin HY, Lee GY, Park HR, Yang SK, Chung HT, Pae HO, Kim HM, Chae SW, Kim HR. 2006. Carbon monoxide and nitric oxide protect against tumor necrosis factor-alpha-induced apoptosis in osteoblasts: HO-1 is necessary to mediate the protection. Clin Chim Acta 365(1-2):270-278. Chaea HJ, Kim HR, Kang YJ, Hyun KC, Kim HJ, Seo HG, Lee JH, Yun-Choi HS, Chang KC. 2007. Heme oxygenase-1 induction by (S)-enantiomer of YS-51 (YS-51S), a synthetic isoquinoline alkaloid, inhibits nitric oxide production and nuclear factor-kappaB translocation in ROS 17/2.8 cells activated with inflammatory stimulants. Int Immunopharmacol 7(12):1559-1568. Chambers TJ, Fuller K, Darby JA, Pringle JA, Horton MA. 1986. Monoclonal antibodies against osteoclasts inhibit bone resorption in vitro. Bone Miner 1(2):127-135. Choi BM, Kim HJ, Oh GS, Pae HO, Oh H, Jeong S, Kwon TO, Kim YM, Chung HT. 2002. 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose protects rat neuronal cells (Neuro 2A) from hydrogen peroxide-mediated cell death via the induction of heme oxygenase-1. Neurosci Lett 328(2):185-189. Chow JW, Fox SW, Lean JM, Chambers TJ. 1998. Role of nitric oxide and prostaglandins in mechanically induced bone formation. J Bone Miner Res 13(6):1039-1044. Choy EH, Panayi GS. 2001. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 344(12):907-916. Clover J, Dodds RA, Gowen M. 1992. Integrin subunit expression by human osteoblasts and osteoclasts in situ and in culture. J Cell Sci 103 ( Pt 1):267-271. Davies J, Warwick J, Totty N, Philp R, Helfrich M, Horton M. 1989. The osteoclast functional antigen, implicated in the regulation of bone resorption, is biochemically related to the vitronectin receptor. J Cell Biol 109(4 Pt 1):1817-1826. de Alvaro C, Teruel T, Hernandez R, Lorenzo M. 2004. Tumor necrosis factor alpha produces insulin resistance in skeletal muscle by activation of inhibitor kappaB kinase in a p38 MAPK-dependent manner. J Biol Chem 279(17):17070-17078. DeRusso PA, Spevak MR, Schwarz KB. 2003. Fractures in biliary atresia misinterpreted as child abuse. Pediatrics 112(1 Pt 1):185-188. DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M. 1997. A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature 388(6642):548-554. Domek-Lopacinska K, Strosznajder JB. 2005. Cyclic GMP metabolism and its role in brain physiology. J Physiol Pharmacol 56 Suppl 2:15-34. Dore S, Takahashi M, Ferris CD, Zakhary R, Hester LD, Guastella D, Snyder SH. 1999. Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury. Proc Natl Acad Sci U S A 96(5):2445-2450. El Bekay R, Alvarez M, Monteseirin J, Alba G, Chacon P, Vega A, Martin-Nieto J, Jimenez J, Pintado E, Bedoya FJ, Sobrino F. 2003. Oxidative stress is a critical mediator of the angiotensin II signal in human neutrophils: involvement of mitogen-activated protein kinase, calcineurin, and the transcription factor NF-kappaB. Blood 102(2):662-671. Engleman VW, Nickols GA, Ross FP, Horton MA, Griggs DW, Settle SL, Ruminski PG, Teitelbaum SL. 1997. A peptidomimetic antagonist of the alpha(v)beta3 integrin inhibits bone resorption in vitro and prevents osteoporosis in vivo. J Clin Invest 99(9):2284-2292. Fahmi H, Di Battista JA, Pelletier JP, Mineau F, Ranger P, Martel-Pelletier J. 2001. Peroxisome proliferator--activated receptor gamma activators inhibit interleukin-1beta-induced nitric oxide and matrix metalloproteinase 13 production in human chondrocytes. Arthritis Rheum 44(3):595-607. Finkel T, Holbrook NJ. 2000. Oxidants, oxidative stress and the biology of ageing. Nature 408(6809):239-247. Fisher JE, Caulfield MP, Sato M, Quartuccio HA, Gould RJ, Garsky VM, Rodan GA, Rosenblatt M. 1993. Inhibition of osteoclastic bone resorption in vivo by echistatin, an 'arginyl-glycyl-aspartyl' (RGD)-containing protein. Endocrinology 132(3):1411-1413. Floyd RA. 1999. Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 222(3):236-245. Forwood MR. 1996. Inducible cyclo-oxygenase (COX-2) mediates the induction of bone formation by mechanical loading in vivo. J Bone Miner Res 11(11):1688-1693. Geusens P. 2009. Emerging treatments for postmenopausal osteoporosis - focus on denosumab. Clin Interv Aging 4(1):241-250. Gilroy DW, Colville-Nash PR, Willis D, Chivers J, Paul-Clark MJ, Willoughby DA. 1999. Inducible cyclooxygenase may have anti-inflammatory properties. Nat Med 5(6):698-701. Glass CK, Ogawa S. 2006. Combinatorial roles of nuclear receptors in inflammation and immunity. Nat Rev Immunol 6(1):44-55. Goldring MB. 2000. The role of the chondrocyte in osteoarthritis. Arthritis Rheum 43(9):1916-1926. Gortz B, Hayer S, Tuerck B, Zwerina J, Smolen JS, Schett G. 2005. Tumour necrosis factor activates the mitogen-activated protein kinases p38alpha and ERK in the synovial membrane in vivo. Arthritis Res Ther 7(5):R1140-1147. Grassi F, Tell G, Robbie-Ryan M, Gao Y, Terauchi M, Yang X, Romanello M, Jones DP, Weitzmann MN, Pacifici R. 2007. Oxidative stress causes bone loss in estrogen-deficient mice through enhanced bone marrow dendritic cell activation. Proc Natl Acad Sci U S A 104(38):15087-15092. Guillen M, Megias J, Gomar F, Alcaraz M. 2008. Haem oxygenase-1 regulates catabolic and anabolic processes in osteoarthritic chondrocytes. J Pathol 214(4):515-522. Guo W, Giancotti FG. 2004. Integrin signalling during tumour progression. Nat Rev Mol Cell Biol 5(10):816-826. Hamada Y, Kitazawa S, Kitazawa R, Fujii H, Kasuga M, Fukagawa M. 2007. Histomorphometric analysis of diabetic osteopenia in streptozotocin-induced diabetic mice: a possible role of oxidative stress. Bone 40(5):1408-1414. Harada S, Rodan GA. 2003. Control of osteoblast function and regulation of bone mass. Nature 423(6937):349-355. Harms JF, Welch DR, Samant RS, Shevde LA, Miele ME, Babu GR, Goldberg SF, Gilman VR, Sosnowski DM, Campo DA, Gay CV, Budgeon LR, Mercer R, Jewell J, Mastro AM, Donahue HJ, Erin N, Debies MT, Meehan WJ, Jones AL, Mbalaviele G, Nickols A, Christensen ND, Melly R, Beck LN, Kent J, Rader RK, Kotyk JJ, Pagel MD, Westlin WF, Griggs DW. 2004. A small molecule antagonist of the alpha(v)beta3 integrin suppresses MDA-MB-435 skeletal metastasis. Clin Exp Metastasis 21(2):119-128. Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F. 2001. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res 16(9):1575-1582. Hikiji H, Shin WS, Koizumi T, Takato T, Susami T, Koizumi Y, Okai-Matsuo Y, Toyo-Oka T. 2000. Peroxynitrite production by TNF-alpha and IL-1beta: implication for suppression of osteoblastic differentiation. Am J Physiol Endocrinol Metab 278(6):E1031-1037. Horton MA, Taylor ML, Arnett TR, Helfrich MH. 1991. Arg-Gly-Asp (RGD) peptides and the anti-vitronectin receptor antibody 23C6 inhibit dentine resorption and cell spreading by osteoclasts. Exp Cell Res 195(2):368-375. Hung SY, Liou HC, Kang KH, Wu RM, Wen CC, Fu WM. 2008. Overexpression of heme oxygenase-1 protects dopaminergic neurons against 1-methyl-4-phenylpyridinium-induced neurotoxicity. Mol Pharmacol 74(6):1564-1575. Iwaniec UT, Moore K, Rivera MF, Myers SE, Vanegas SM, Wronski TJ. 2007. A comparative study of the bone-restorative efficacy of anabolic agents in aged ovariectomized rats. Osteoporos Int 18(3):351-362. Jackson SM, Demer LL. 2000. Peroxisome proliferator-activated receptor activators modulate the osteoblastic maturation of MC3T3-E1 preosteoblasts. FEBS Lett 471(1):119-124. Janes CH, Dickson ER, Okazaki R, Bonde S, McDonagh AF, Riggs BL. 1995. Role of hyperbilirubinemia in the impairment of osteoblast proliferation associated with cholestatic jaundice. J Clin Invest 95(6):2581-2586. Jeon MJ, Kim JA, Kwon SH, Kim SW, Park KS, Park SW, Kim SY, Shin CS. 2003. Activation of peroxisome proliferator-activated receptor-gamma inhibits the Runx2-mediated transcription of osteocalcin in osteoblasts. J Biol Chem 278(26):23270-23277. Juan SH, Lee TS, Tseng KW, Liou JY, Shyue SK, Wu KK, Chau LY. 2001. Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E-deficient mice. Circulation 104(13):1519-1525. Kadono H, Kido J, Kataoka M, Yamauchi N, Nagata T. 1999. Inhibition of osteoblastic cell differentiation by lipopolysaccharide extract from Porphyromonas gingivalis. Infect Immun 67(6):2841-2846. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O'Neill MC, Zinman B, Viberti G. 2006. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 355(23):2427-2443. Kamata H, Hirata H. 1999. Redox regulation of cellular signalling. Cell Signal 11(1):1-14. Kanis JA. 1997. Diagnosis of osteoporosis. Osteoporos Int 7 Suppl 3:S108-116. Kawaguchi H, Akune T, Yamaguchi M, Ohba S, Ogata N, Chung UI, Kubota N, Terauchi Y, Kadowaki T, Nakamura K. 2005. Distinct effects of PPARgamma insufficiency on bone marrow cells, osteoblasts, and osteoclastic cells. J Bone Miner Metab 23(4):275-279. Kawahito Y, Kondo M, Tsubouchi Y, Hashiramoto A, Bishop-Bailey D, Inoue K, Kohno M, Yamada R, Hla T, Sano H. 2000. 15-deoxy-delta(12,14)-PGJ(2) induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats. J Clin Invest 106(2):189-197. Kawata A, Mikuni-Takagaki Y. 1998. Mechanotransduction in stretched osteocytes--temporal expression of immediate early and other genes. Biochem Biophys Res Commun 246(2):404-408. Kawatani M, Osada H. 2009. Osteoclast-targeting small molecules for the treatment of neoplastic bone metastases. Cancer Sci 100(11):1999-2005. Kersten S, Desvergne B, Wahli W. 2000. Roles of PPARs in health and disease. Nature 405(6785):421-424. Khan E, Abu-Amer Y. 2003. Activation of peroxisome proliferator-activated receptor-gamma inhibits differentiation of preosteoblasts. J Lab Clin Med 142(1):29-34. Khosla S, Westendorf JJ, Oursler MJ. 2008. Building bone to reverse osteoporosis and repair fractures. J Clin Invest 118(2):421-428. Kim DH, Kim JH, Kim EH, Na HK, Cha YN, Chung JH, Surh YJ. 2009. 15-Deoxy-Delta12,14-prostaglandin J2 upregulates the expression of heme oxygenase-1 and subsequently matrix metalloproteinase-1 in human breast cancer cells: possible roles of iron and ROS. Carcinogenesis 30(4):645-654. Kim EJ, Park KS, Chung SY, Sheen YY, Moon DC, Song YS, Kim KS, Song S, Yun YP, Lee MK, Oh KW, Yoon DY, Hong JT. 2003. Peroxisome proliferator-activated receptor-gamma activator 15-deoxy-Delta12,14-prostaglandin J2 inhibits neuroblastoma cell growth through induction of apoptosis: association with extracellular signal-regulated kinase signal pathway. J Pharmacol Exp Ther 307(2):505-517. Kim SW, Her SJ, Kim SY, Shin CS. 2005. Ectopic overexpression of adipogenic transcription factors induces transdifferentiation of MC3T3-E1 osteoblasts. Biochem Biophys Res Commun 327(3):811-819. Koh SH, Jung B, Song CW, Kim Y, Kim YS, Kim SH. 2005. 15-Deoxy-delta12,14-prostaglandin J2, a neuroprotectant or a neurotoxicant? Toxicology 216(2-3):232-243. 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. 1998. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93(2):165-176. Le WD, Xie WJ, Appel SH. 1999. Protective role of heme oxygenase-1 in oxidative stress-induced neuronal injury. J Neurosci Res 56(6):652-658. Lecka-Czernik B, Gubrij I, Moerman EJ, Kajkenova O, Lipschitz DA, Manolagas SC, Jilka RL. 1999. Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPARgamma2. J Cell Biochem 74(3):357-371. Lecka-Czernik B, Moerman EJ, Grant DF, Lehmann JM, Manolagas SC, Jilka RL. 2002. Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation. Endocrinology 143(6):2376-2384. Lee TS, Tsai HL, Chau LY. 2003. Induction of heme oxygenase-1 expression in murine macrophages is essential for the anti-inflammatory effect of low dose 15-deoxy-Delta 12,14-prostaglandin J2. J Biol Chem 278(21):19325-19330. Leesnitzer LM, Parks DJ, Bledsoe RK, Cobb JE, Collins JL, Consler TG, Davis RG, Hull-Ryde EA, Lenhard JM, Patel L, Plunket KD, Shenk JL, Stimmel JB, Therapontos C, Willson TM, Blanchard SG. 2002. Functional consequences of cysteine modification in the ligand binding sites of peroxisome proliferator activated receptors by GW9662. Biochemistry 41(21):6640-6650. Li M, Ke HZ, Qi H, Healy DR, Li Y, Crawford DT, Paralkar VM, Owen TA, Cameron KO, Lefker BA, Brown TA, Thompson DD. 2003. A novel, non-prostanoid EP2 receptor-selective prostaglandin E2 agonist stimulates local bone formation and enhances fracture healing. J Bone Miner Res 18(11):2033-2042. Li M, Kim DH, Tsenovoy PL, Peterson SJ, Rezzani R, Rodella LF, Aronow WS, Ikehara S, Abraham NG. 2008. Treatment of obese diabetic mice with a heme oxygenase inducer reduces visceral and subcutaneous adiposity, increases adiponectin levels, and improves insulin sensitivity and glucose tolerance. Diabetes 57(6):1526-1535. Liacini A, Sylvester J, Li WQ, Zafarullah M. 2002. Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1 (AP-1) and nuclear factor kappa B (NF-kappa B) transcription factors down-regulates matrix metalloproteinase gene expression in articular chondrocytes. Matrix Biol 21(3):251-262. Lin TH, Yang RS, Tang CH, Wu MY, Fu WM. 2008. Regulation of the maturation of osteoblasts and osteoclastogenesis by glutamate. Eur J Pharmacol 589(1-3):37-44. Lin YT, Tang CH, Chuang WJ, Wang SM, Huang TF, Fu WM. 2005. Inhibition of adipogenesis by RGD-dependent disintegrin. Biochem Pharmacol 70(10):1469-1478. Luppen CA, Leclerc N, Noh T, Barski A, Khokhar A, Boskey AL, Smith E, Frenkel B. 2003. Brief bone morphogenetic protein 2 treatment of glucocorticoid-inhibited MC3T3-E1 osteoblasts rescues commitment-associated cell cycle and mineralization without alteration of Runx2. J Biol Chem 278(45):44995-45003. Maines MD. 1988. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 2(10):2557-2568. Mangelsdorf DJ, Evans RM. 1995. The RXR heterodimers and orphan receptors. Cell 83(6):841-850. McHugh KP, Hodivala-Dilke K, Zheng MH, Namba N, Lam J, Novack D, Feng X, Ross FP, Hynes RO, Teitelbaum SL. 2000. Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts. J Clin Invest 105(4):433-440. Mendez M, LaPointe MC. 2003. PPARgamma inhibition of cyclooxygenase-2, PGE2 synthase, and inducible nitric oxide synthase in cardiac myocytes. Hypertension 42(4):844-850. Mengshol JA, Vincenti MP, Coon CI, Barchowsky A, Brinckerhoff CE. 2000. Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor kappaB: differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum 43(4):801-811. Michalik L, Wahli W. 2006. Involvement of PPAR nuclear receptors in tissue injury and wound repair. J Clin Invest 116(3):598-606. Mody N, Parhami F, Sarafian TA, Demer LL. 2001. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med 31(4):509-519. Moerman EJ, Teng K, Lipschitz DA, Lecka-Czernik B. 2004. Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell 3(6):379-389. Morse D, Lin L, Choi AM, Ryter SW. 2009. Heme oxygenase-1, a critical arbitrator of cell death pathways in lung injury and disease. Free Radic Biol Med 47(1):1-12. Motterlini R, Clark JE, Foresti R, Sarathchandra P, Mann BE, Green CJ. 2002. Carbon monoxide-releasing molecules: characterization of biochemical and vascular activities. Circ Res 90(2):E17-24. Mukai T, Otsuka F, Otani H, Yamashita M, Takasugi K, Inagaki K, Yamamura M, Makino H. 2007. TNF-alpha inhibits BMP-induced osteoblast differentiation through activating SAPK/JNK signaling. Biochem Biophys Res Commun 356(4):1004-1010. Mundy GR. 2002. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2(8):584-593. Murphy MG, Cerchio K, Stoch SA, Gottesdiener K, Wu M, Recker R. 2005. Effect of L-000845704, an alphaVbeta3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab 90(4):2022-2028. Nakamura I, Duong le T, Rodan SB, Rodan GA. 2007. Involvement of alpha(v)beta3 integrins in osteoclast function. J Bone Miner Metab 25(6):337-344. Nakamura I, Tanaka H, Rodan GA, Duong LT. 1998. Echistatin inhibits the migration of murine prefusion osteoclasts and the formation of multinucleated osteoclast-like cells. Endocrinology 139(12):5182-5193. Nuttall ME, Gimble JM. 2004. Controlling the balance between osteoblastogenesis and adipogenesis and the consequent therapeutic implications. Curr Opin Pharmacol 4(3):290-294. Nuttall ME, Patton AJ, Olivera DL, Nadeau DP, Gowen M. 1998. Human trabecular bone cells are able to express both osteoblastic and adipocytic phenotype: implications for osteopenic disorders. J Bone Miner Res 13(3):371-382. Ogawa S, Urano T, Hosoi T, Miyao M, Hoshino S, Fujita M, Shiraki M, Orimo H, Ouchi Y, Inoue S. 1999. Association of bone mineral density with a polymorphism of the peroxisome proliferator-activated receptor gamma gene: PPARgamma expression in osteoblasts. Biochem Biophys Res Commun 260(1):122-126. Otterbein LE, Soares MP, Yamashita K, Bach FH. 2003. Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol 24(8):449-455. Pan W, Quarles LD, Song LH, Yu YH, Jiao C, Tang HB, Jiang CH, Deng HW, Li YJ, Zhou HH, Xiao ZS. 2005. Genistein stimulates the osteoblastic differentiation via NO/cGMP in bone marrow culture. J Cell Biochem 94(2):307-316. Parfitt AM, Villanueva AR, Foldes J, Rao DS. 1995. Relations between histologic indices of bone formation: implications for the pathogenesis of spinal osteoporosis. J Bone Miner Res 10(3):466-473. Park SR, Oreffo RO, Triffitt JT. 1999. Interconversion potential of cloned human marrow adipocytes in vitro. Bone 24(6):549-554. Pataki A, Muller K, Green JR, Ma YF, Li QN, Jee WS. 1997. Effects of short-term treatment with the bisphosphonates zoledronate and pamidronate on rat bone: a comparative histomorphometric study on the cancellous bone formed before, during, and after treatment. Anat Rec 249(4):458-468. Pei L, Tontonoz P. 2004. Fat's loss is bone's gain. J Clin Invest 113(6):805-806. Pelletier JP, Martel-Pelletier J, Abramson SB. 2001. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum 44(6):1237-1247. Poole AR. 1999. An introduction to the pathophysiology of osteoarthritis. Front Biosci 4:D662-670. Poss KD, Tonegawa S. 1997. Reduced stress defense in heme oxygenase 1-deficient cells. Proc Natl Acad Sci U S A 94(20):10925-10930. Raisz LG. 2005. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 115(12):3318-3325. Rawlinson SC, Zaman G, Mosley JR, Pitsillides AA, Lanyon LE. 1998. Heme oxygenase isozymes in bone: induction of HO-1 mRNA following physiological levels of mechanical loading in vivo. Bone 23(5):433-436. Reher P, Harris M, Whiteman M, Hai HK, Meghji S. 2002. Ultrasound stimulates nitric oxide and prostaglandin E2 production by human osteoblasts. Bone 31(1):236-241. Reijman M, Bierma-Zeinstra SM, Pols HA, Koes BW, Stricker BH, Hazes JM. 2005. Is there an association between the use of different types of nonsteroidal antiinflammatory drugs and radiologic progression of osteoarthritis? The Rotterdam Study. Arthritis Rheum 52(10):3137-3142. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. 1998. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391(6662):79-82. Rodan GA, Martin TJ. 2000. Therapeutic approaches to bone diseases. Science 289(5484):1508-1514. Rojo AI, Salina M, Salazar M, Takahashi S, Suske G, Calvo V, de Sagarra MR, Cuadrado A. 2006. Regulation of heme oxygenase-1 gene expression through the phosphatidylinositol 3-kinase/PKC-zeta pathway and Sp1. Free Radic Biol Med 41(2):247-261. Rosen ED, Spiegelman BM. 2001. PPARgamma : a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem 276(41):37731-37734. Rossi A, Kapahi P, Natoli G, Takahashi T, Chen Y, Karin M, Santoro MG. 2000. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinase. Nature 403(6765):103-108. Ryoo HM, Lee MH, Kim YJ. 2006. Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Gene 366(1):51-57. Ryter SW, Alam J, Choi AM. 2006. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev 86(2):583-650. Scher JU, Pillinger MH. 2005. 15d-PGJ2: the anti-inflammatory prostaglandin? Clin Immunol 114(2):100-109. Schipper HM. 2000. Heme oxygenase-1: role in brain aging and neurodegeneration. Exp Gerontol 35(6-7):821-830. Serni U, Mannoni A, Benucci M. 1999. Is there preliminary in-vivo evidence for an influence of nonsteroidal antiinflammatory drugs on progression in osteoarthritis? Part II-evidence from animal models. Osteoarthritis Cartilage 7(3):351-352. Simonin MA, Bordji K, Boyault S, Bianchi A, Gouze E, Becuwe P, Dauca M, Netter P, Terlain B. 2002. PPAR-gamma ligands modulate effects of LPS in stimulated rat synovial fibroblasts. Am J Physiol Cell Physiol 282(1):C125-133. Skuli N, Monferran S, Delmas C, Favre G, Bonnet J, Toulas C, Cohen-Jonathan Moyal E. 2009. Alphavbeta3/alphavbeta5 integrins-FAK-RhoB: a novel pathway for hypoxia regulation in glioblastoma. Cancer Res 69(8):3308-3316. Soroceanu MA, Miao D, Bai XY, Su H, Goltzman D, Karaplis AC. 2004. Rosiglitazone impacts negatively on bone by promoting osteoblast/osteocyte apoptosis. J Endocrinol 183(1):203-216. Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN. 1987. Bilirubin is an antioxidant of possible physiological importance. Science 235(4792):1043-1046. Straus DS, Pascual G, Li M, Welch JS, Ricote M, Hsiang CH, Sengchanthalangsy LL, Ghosh G, Glass CK. 2000. 15-deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-kappa B signaling pathway. Proc Natl Acad Sci U S A 97(9):4844-4849. Sun HB, Yokota H. 2002. Reduction of cytokine-induced expression and activity of MMP-1 and MMP-13 by mechanical strain in MH7A rheumatoid synovial cells. Matrix Biol 21(3):263-270. Tang CH, Chiu YC, Tan TW, Yang RS, Fu WM. 2007. Adiponectin enhances IL-6 production in human synovial fibroblast via an AdipoR1 receptor, AMPK, p38, and NF-kappa B pathway. J Immunol 179(8):5483-5492. Tang CH, Yang RS, Fu WM. 2005. Prostaglandin E2 stimulates fibronectin expression through EP1 receptor, phospholipase C, protein kinase Calpha, and c-Src pathway in primary cultured rat osteoblasts. J Biol Chem 280(24):22907-22916. Tang CH, Yang RS, Huang TH, Lu DY, Chuang WJ, Huang TF, Fu WM. 2006. Ultrasound stimulates cyclooxygenase-2 expression and increases bone formation through integrin, focal adhesion kinase, phosphatidylinositol 3-kinase, and Akt pathway in osteoblasts. Mol Pharmacol 69(6):2047-2057. Thompson JE, Phillips RJ, Erdjument-Bromage H, Tempst P, Ghosh S. 1995. I kappa B-beta regulates the persistent response in a biphasic activation of NF-kappa B. Cell 80(4):573-582. Ueta Y, Fujihara H, Serino R, Dayanithi G, Ozawa H, Matsuda K, Kawata M, Yamada J, Ueno S, Fukuda A, Murphy D. 2005. Transgenic expression of enhanced green fluorescent protein enables direct visualization for physiological studies of vasopressin neurons and isolated nerve terminals of the rat. Endocrinology 146(1):406-413. Uretmen S, Gol M, Cimrin D, Irmak E. 2005. Effects of chronic liver disease on bone mineral density and bone metabolism markers in postmenopausal women. Eur J Obstet Gynecol Reprod Biol 123(1):67-71. Wang FS, Kuo YR, Wang CJ, Yang KD, Chang PR, Huang YT, Huang HC, Sun YC, Yang YJ, Chen YJ. 2004. Nitric oxide mediates ultrasound-induced hypoxia-inducible factor-1alpha activation and vascular endothelial growth factor-A expression in human osteoblasts. Bone 35(1):114-123. Weinreb M, Pollak RD, Ackerman Z. 2004. Experimental cholestatic liver disease through bile-duct ligation in rats results in skeletal fragility and impaired osteoblastogenesis. J Hepatol 40(3):385-390. Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K, Charo I, Leibel RL, Ferrante AW, Jr. 2006. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 116(1):115-124. Weisiger RA, Ostrow JD, Koehler RK, Webster CC, Mukerjee P, Pascolo L, Tiribelli C. 2001. Affinity of human serum albumin for bilirubin varies with albumin concentration and buffer composition: results of a novel ultrafiltration method. J Biol Chem 276(32):29953-29960. Yang RS, Tang CH, Chuang WJ, Huang TH, Peng HC, Huang TF, Fu WM. 2005. Inhibition of tumor formation by snake venom disintegrin. Toxicon 45(5):661-669. Yeh CH, Peng HC, Yang RS, Huang TF. 2001. Rhodostomin, a snake venom disintegrin, inhibits angiogenesis elicited by basic fibroblast growth factor and suppresses tumor growth by a selective alpha(v)beta(3) blockade of endothelial cells. Mol Pharmacol 59(5):1333-1342. Yoshino T, Yamaguchi I. 1996. Bone mineral density at the metaphysis is specifically reduced in STZ-treated diabetic rats. Life Sci 59(2):161-168. Zaragoza C, Lopez-Rivera E, Garcia-Rama C, Saura M, Martinez-Ruiz A, Lizarbe TR, Martin-de-Lara F, Lamas S. 2006. Cbfa-1 mediates nitric oxide regulation of MMP-13 in osteoblasts. J Cell Sci 119(Pt 9):1896-1902. Zayed N, Afif H, Chabane N, Mfuna-Endam L, Benderdour M, Martel-Pelletier J, Pelletier JP, Motiani RK, Trebak M, Duval N, Fahmi H. 2008. Inhibition of interleukin-1beta-induced matrix metalloproteinases 1 and 13 production in human osteoarthritic chondrocytes by prostaglandin D2. Arthritis Rheum 58(11):3530-3540. Zhang X, Schwarz EM, Young DA, Puzas JE, Rosier RN, O'Keefe RJ. 2002. Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair. J Clin Invest 109(11):1405-1415. Zhao H, Kitaura H, Sands MS, Ross FP, Teitelbaum SL, Novack DV. 2005. Critical role of beta3 integrin in experimental postmenopausal osteoporosis. J Bone Miner Res 20(12):2116-2123. Zwerina J, Tzima S, Hayer S, Redlich K, Hoffmann O, Hanslik-Schnabel B, Smolen JS, Kollias G, Schett G. 2005. Heme oxygenase 1 (HO-1) regulates osteoclastogenesis and bone resorption. FASEB J 19(14):2011-2013. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/45243 | - |
| dc.description.abstract | 核內受體，過氧化體增殖劑活化受體γ(peroxisome proliferators-activated receptor gamma, PPARγ)被視為是一種抑制骨合成的因子，因為PPARγ會增加脂肪細胞的形成以及直接抑制造骨細胞，而引發老年性骨質疏鬆症。我們發現到餵食大鼠PPARγ配體(活化劑) rosiglitazone會降低大鼠脛骨之骨密度以及血清中鹼性磷酸酶(ALP)的表現，但是並不影響與骨代謝相關的血鈣以及破骨細胞指標CTx。我們進一步使用兩種PPARγ活化劑，包括ciglitazone以及體內可自行合成的15d-PGJ2，來驗證PPARγ活化劑抑制骨合成的機轉。我們的研究指出在初級造骨細胞中，PPARγ活化劑會抑制造骨細胞的鈣化能力以及鹼性磷酸酶(ALP)的活性。我們接著利用反轉錄酶連鎖反應中(RT-PCR)，發現ciglitazone和15d-PGJ2會抑制造骨細胞表現骨形成蛋白第二型(BMP-2)以及骨鈣素(OCN)。更進一步地，PPARγ活化劑會抑制轉錄因子NF-κB所調控的兩個造骨相關蛋白：環氧化酶二型(COX-2)和誘導型一氧化氮合成酶(iNOS)的表現。利用治療性超音波來刺激造骨細胞可誘導造骨細胞表現COX-2以及iNOS和一氧化氮，然而在PPARγ活化劑的存在下會中止治療性超音波的作用。在動物實驗中，我們利用局部注射的方法在年輕大鼠的脛骨遠端注射PPARγ活化劑，而PPARγ活化劑會降低次級海綿骨的骨容積。這些結果證實，PPARγ活化劑會直接抑制造骨細胞的分化以及會抑制造骨細胞所表現的多種骨合成促進因子。本研究可以用來解釋年長者以及服用thiazolidinediones (TZD)類藥物的糖尿病患易得到骨質疏鬆症的原因。
第一型血基質氧化酵素(heme oxygenase-1, HO-1)能夠將血基質(heme)代謝成一氧化氮、膽綠素(biliverdin)以及鐵離子，HO-1在血管疾病、器官移植以及發炎反應中扮演重要角色。在骨組織中，有報告指出過度表現HO-1會抑制破骨細胞的形成。然而HO-1對於造骨細胞的作用仍是未知。本研究利用攜帶人類HO-1基因的腺病毒以及HO-1的誘導劑hemin來探討HO-1在初級造骨細胞中的作用。我們發現過度表現HO-1會抑制造骨細胞的鈣化能力以及鹼性磷酸酶(ALP)的活性，並且會抑制多種造骨細胞分化指標如鹼性磷酸酶、骨鈣素(OCN)以及轉譯因子RUNX2。我們也發現到HO-1的三個下游：一氧化碳、膽色素(bilirubin)以及鐵離子均參與HO-1對於造骨細胞分化的抑制作用。在造骨細胞中，HO-1可以被雙氧水(H2O2)、內毒素(LPS)以及發炎性細胞介素(cytokine)包含IL-1β以及TNF-α所誘導。在動物實驗中我們也在鏈菌素(streptozotocin, STZ)所誘發的糖尿病小鼠中，在造骨細胞上觀察到HO-1的表現。我們進一步發現到15d-PGJ2在造骨細胞中會經由PI3K-Akt以及MAPK訊息路徑來大量表現HO-1。利用HO-1抑制劑ZnPP IX可以拮抗hemin以及15d-PGJ2對造骨細胞所表現骨鈣素的抑制。我們的研究證實誘導HO-1表現會抑制造骨細胞的分化及成熟且可能參與氧化壓力以及發炎所造成的骨流失。 組合蛋白(integrins)是一群異型二聚體的(heterodimeric)穿膜受體，可以調控細胞與細胞間以及細胞與基質間的交互作用。αvβ3組合蛋白是玻璃體結合蛋白(vitronectin)以及骨橋蛋白(osteopontin)的受體，αvβ3大量表現於破骨細胞並且參與破骨細胞的貼附、活化以及破骨細胞在骨表面上的轉移。在細胞實驗以及動物實驗中，利用αvβ3的拮抗劑例如:含有精氨酸(Arg)-甘氨酸(Gly)-天門冬安酸(Asp)片段的蛋白藥物、小分子抑制劑以及抑制性抗體均被報導到可以抑制破骨細胞所造成的骨代謝。在本研究中，我們將蛇毒所萃取出來的數種組合蛋白(rhodostomin derivatives)結合人類血清蛋白以增加其生物體內穩定性，這些組合蛋白(HSA-ARLDDL、derivative P、derivative X)對於αvβ3組合蛋白擁有高度的專一性，我們進一步利用這些組合蛋白來研究其在破骨細胞分化以及卵巢切除所造成的骨質疏鬆中所扮演的角色。在破骨細胞分化中，rhodostomin的衍生物顯著地抑制了破骨細胞的形成而且在奈米莫爾濃度的範圍內即可達到半數抑制濃度(IC50)。在破骨細胞分化的後期給予HSA-ARLDDL依舊可以抑制破骨細胞的形成。在卵巢切除小鼠的動物實驗中，每週給予一次HSA-ARLDDL以及derivative P可以顯著地抑制血清中破骨細胞活性指標(CTx)的增加以及脛骨和股骨中海綿骨的流失。而在卵巢切除大鼠中，rhodostomin衍生物亦抑制了血清中破骨細胞活性指標(CTx)的表現以及減緩了髖骨骨密度的流失。本研究指出這些rhodostomin的衍生物對於αvβ3組合蛋白有高度專一性且能在動物體內長時間作用，這些衍生物可以發展為臨床上抑制骨代謝，並治療停經後骨質疏鬆症的藥物。 金屬蛋白酶(matrix metalloproteinase, MMP)中的膠原蛋白酶三型(collagenase-3, MMP-13)在病理情況下的軟骨退化扮演重要的角色。在類風濕性關節炎(RA)以及骨關節炎(OA)的關節組織中可以看到MMP-13的大量表現。而且在這些病症中，滑囊纖維母細胞(synovial fibroblast)會分泌MMP-13以及其他的發炎性細胞介素引起進一步的病症。PPARγ訊息主要調控脂肪形成以及醣類代謝。越來越多證據指出PPARγ在發炎性關節炎中扮演了重要的角色，主要是經由調控B細胞的反應以及在受刺激的滑囊纖維母細胞以及軟骨細胞中抑制MMP-13的產生。然而文獻指出：內生性的PPARγ配體，15d-PGJ2在抑制發炎性關節炎中比其他化學合成的PPARγ活化劑擁有更佳藥效，且其藥效有部份不經由PPARγ的訊息機轉(PPARγ-independent)。然而詳細機轉仍是未知。在本研究中，我們發現15d-PGJ2在人類滑囊纖維母細胞中顯著抑制內毒素(LPS)或TNF-α所誘發的MMP-13的表現。我們進一步地發現到，在滑囊纖維母細胞中，轉錄因子NF-κB在TNF-α誘導MMP-13的表現中扮演重要角色，15d-PGJ2會經由直接抑制IKK的活性來顯著地抑制NF-κB的入核與活化，而這個步驟是不經由PPARγ訊息的。本研究結果指出在發炎的關節中提升15d-PGJ2的含量在臨床上可發展為避免軟骨退化的治療方法。 | zh_TW |
| dc.description.abstract | Peroxisome proliferators-activated receptor gamma (PPARγ), a ligand-activated transcription factor, is considered as an anti-osteoblastic factor associated with adiposity and the elderly osteoporosis due to a defect in osteoblastogenesis. We have found that oral administration of PPARγ activator rosiglitazone decreased tibia BMD and serum ALP but left serum calcium and osteoclast marker c-terminal telopeptide unaffected. In addition, we examined the inhibitory mechanisms of PPARγ on the bone formation by using PPARγ activators ciglitazone and 15-deoxy-Δ12,14-prostaglandin-J2 (15d-PGJ2). Our data indicated that PPARγ ligands inhibited both mineralized bone nodules and alkaline phosphatase (ALP) activities in cultured primary osteoblasts. Reverse transcription polymerase chain reaction (RT-PCR) showed that the expression of bone morphogenetic protein-2 (BMP-2) and osteocalcin (OCN) was inhibited by ciglitizone and 15d-PGJ2. Furthermore, PPARγ ligands inhibited NFκB associated downstream COX-2 and iNOS osteogenic signaling. The ultrasound (US)-induced elevation of COX-2 and iNOS expression and nitric oxide (NO) production were attenuated in the presence of PPARγ ligands. Furthermore, local administration of PPARγ ligands into the metaphysis of rat tibia decreased the bone volume in secondary spongiosa. These results suggest that the activation of PPARγ inhibits osteoblastic differentiation and the expression of several anabolic mediators involved in bone formation. These data may reflect osteoporosis and less bone formation in the aging people and patients treated with thiazolidinediones.
Heme-oxygenase-1 (HO-1), an important enzyme involved in vascular disease, transplantation, and inflammation, catalyzes the degradation of heme into carbon monoxide and biliverdin. It has been reported that overexpression of HO-1 inhibits osteoclastogenesis. However, the effect of HO-1 on osteoblast differentiation is still not clear. We here used adenoviral vector expressing recombinant human HO-1 and HO-1 inducer hemin to study the effects of HO-1 in primary cultured osteoblasts. The results showed that induction of HO-1 inhibited the maturation of osteoblasts including mineralized bone nodule formation, alkaline phosphatase activity and decreased mRNA expression of several differentiation markers such as alkaline phosphatase, osteocalcin, and RUNX2. Furthermore, downstream products of HO-1, bilirubin, carbon monoxide and iron, are involved in the inhibitory action of HO-1. HO-1 can be induced by H2O2, lipopolysaccharide (LPS) and inflammatory cytokines such as TNF-α and IL-1β in osteoblasts and also in STZ-induced diabetic mice. In addition, endogenous PPARγ ligand, 15d-PGJ2 markedly increased both mRNA and protein levels of HO-1 in osteoblasts via PI3K-Akt and MAPK pathways. Blockade of HO activity by ZnPP IX antagonized the inhibitory action on osteocalcin expression by hemin and 15d-PGJ2. Our results indicate that upregulation of HO-1 inhibits the maturation of osteoblasts and HO-1 may be involved in oxidative- or inflammation-induced bone loss. Integrins are heterodimeric cell surface receptors which mediate cell-cell and cell-matrix interaction. The vitronectin and osteopontin receptors, αvβ3 integrin, is highly expressed and implicated in the adhesion, activation and migration of osteoclasts on the bone surface as well as osteoclast polarization. αvβ3 integrin plays an important role in osteoclast differentiation and resorption. In addition, Arg-Gly-Asp (RGD)-containing peptides, small molecular inhibitors and blocking antibodies to αvβ3 integrin have been shown to inhibit bone resorption in vitro and in vivo. In this study, we examined the effects disintegrins, derivatives of rhodostomin conjugated with human serum albumin (HSA-ARLDDL, derivative P and derivative X) and highly selective to αvβ3, on RANKL-induced osteoclastogenesis and ovariectomy (OVX)-induced osteoporosis. In RANKL-induced osteoclastogenesis, derivatives of rhodostomin significantly inhibited osteoclast formation and IC50 was at nM range. Post-treatment of HSA-ARLDDL also inhibits osteoclast formation. Furthermore, weekly administration of HSA-ARLDDL and derivative P significantly inhibited the increase of serum bone resorption marker and decrease of cancellous bone loss in tibia and femur induced in OVX mice. Rhodostomin derivatives also decreased bone resorption markers and ameliorated the reduction of total hip BMD in OVX rats. These results suggest that the highly selective and long-duration of αvβ3 integrin antagonists, rhodostomin derivatives, could be developed for effective drugs for the treatment of postmenopausal osteoporosis. Matrix metalloproteinase (MMP) of collagenase-3 (MMP-13) plays an important role in the degradation of cartilage in pathologic conditions. MMP-13 is found to be elevated in joint tissues in both rheumatoid arthritis (RA) and osteoarthritis (OA) patients. In addition, inflammation-stimulated synovial fibroblasts are able to release MMP-13 and other cytokines related to these syndromes. PPARγ signaling controls adipogenesis and glucose metabolism. A growing evidence indicated that PPARγ plays a critical role in inflammatory arthritis by regulating B cell response and inhibiting MMP-13 production in stimulated synovial fibroblasts and chondrocytes and natural PPARγ ligand, 15d-PGJ2 is reported to be more potent than other synthetic PPARγ compounds in the inhibition of inflammatory arthritis. 15d-PGJ2 may exert its effects via PPARγ-dependent and also PPARγ-independent pathways. In this study, it was found that 15d-PGJ2 markedly inhibited LPS- and TNF-α-induced MMP-13 production in human synovial fibroblasts. In addition, activation of nuclear factor κB (NF-κB) is strongly associated with MMP-13 induction by TNF-α and 15d-PGJ2 markedly attenuated the translocation of NF-κB by direct inhibition of the activation of IKK via a PPARγ-independent manner. These results indicate that elevation of 15d-PGJ2 levels in the inflammatory joint disease may have therapeutic potential in the prevention of cartilage degradation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T04:10:28Z (GMT). No. of bitstreams: 1 ntu-99-D93443005-1.pdf: 7081998 bytes, checksum: f72bac087a377420445226a34cb0bf85 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | Abbreviations 1
Abstract in Chinese 4 Abstract in English 8 Chapter 1. Introduction 13 Chapter 2. Materials and Methods 44 Chapter 3. PPARγ inhibits osteogenesis via the down-regulation of the expression of COX-2 and iNOS in rats ……….. 60 Chapter 4. Upregulation of heme oxygenase-1 inhibits the maturation and mineralization of osteoblasts ………. 88 Chapter 5. Inhibition of osteoporosis by the rhodostomin variants of αvβ3 integrin antagonist ………………………… 122 Chapter 6. 15-deoxy-Δ12,14-prostaglandin-J2 inhibits inflammation-induced matrix metalloproteinase 13 production via the antagonism of NF-κB activation in human synovial fibroblasts ………………………….. 156 Chapter 7. Conclusion and Perspective 180 References 186 Publications and Honors 206 | |
| dc.language.iso | en | |
| dc.subject | 第一型血基質氧化酵素 | zh_TW |
| dc.subject | 造骨細胞 | zh_TW |
| dc.subject | 破骨細胞 | zh_TW |
| dc.subject | 去組合蛋白 | zh_TW |
| dc.subject | PPARγ | zh_TW |
| dc.subject | osteoblast | en |
| dc.subject | heme oxygenase-1 | en |
| dc.subject | PPARγ | en |
| dc.subject | disintegrin | en |
| dc.subject | osteoclast | en |
| dc.title | PPARγ配體、第一型血基質氧化酵素與去組合蛋白在調控骨代謝與發炎之探討 | zh_TW |
| dc.title | Studies of PPARγ ligands, heme oxygenase-1, and disintegrin in bone metabolism and inflammation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.coadvisor | 楊榮森(Rong-Sen Yang) | |
| dc.contributor.oralexamcommittee | 劉興華(Shing-Hwa Liu),楊春茂(Chuen-Mao Yang),莊偉哲(Woei-Jer Chuang) | |
| dc.subject.keyword | 造骨細胞,破骨細胞,去組合蛋白,PPARγ,第一型血基質氧化酵素, | zh_TW |
| dc.subject.keyword | osteoblast,osteoclast,disintegrin,PPARγ,heme oxygenase-1, | en |
| dc.relation.page | 208 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-01-29 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥理學研究所 | zh_TW |
| 顯示於系所單位： | 藥理學科所 | |
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