請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37357完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊偉勛(Wei-Shiung Yang) | |
| dc.contributor.author | SHU-PING YANG | en |
| dc.contributor.author | 楊淑萍 | zh_TW |
| dc.date.accessioned | 2021-06-13T15:25:26Z | - |
| dc.date.available | 2013-08-08 | |
| dc.date.copyright | 2008-08-08 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-07-18 | |
| dc.identifier.citation | 1. Newman, A.M., Arthritis and sexuality. Nurs Clin North Am, 2007. 42(4): p.
621-30; vii. 2. Felson, D.T., Clinical practice. Osteoarthritis of the knee. N Engl J Med, 2006. 354(8): p. 841-8. 3. Altman, R., et al., Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum, 1986. 29(8): p. 1039-49. 4. Brandt, K.D., et al., Yet more evidence that osteoarthritis is not a cartilage disease. Ann Rheum Dis, 2006. 65(10): p. 1261-4. 5. Dijkgraaf, L.C., et al., The structure, biochemistry, and metabolism of osteoarthritic cartilage: a review of the literature. J Oral Maxillofac Surg, 1995. 53(10): p. 1182-92. 6. Poole, A.R., et al., Composition and structure of articular cartilage: a template for tissue repair. Clin Orthop Relat Res, 2001(391 Suppl): p. S26-33. 7. Eyre, D., Collagen of articular cartilage. Arthritis Res, 2002. 4(1): p. 30-5. 8. Maroudas, A., et al., Aggrecan turnover in human articular cartilage: use of aspartic acid racemization as a marker of molecular age. Arch Biochem Biophys, 1998. 350(1): p. 61-71. 9. Watanabe, H., Y. Yamada, and K. Kimata, Roles of aggrecan, a large chondroitin sulfate proteoglycan, in cartilage structure and function. J Biochem, 1998. 124(4): p. 687-93. 10. Dominici, M., T.J. Hofmann, and E.M. Horwitz, Bone marrow mesenchymal cells: biological properties and clinical applications. J Biol Regul Homeost Agents, 2001. 15(1): p. 28-37. 11. Bianco, P., et al., Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells, 2001. 19(3): p. 180-92. 12. Goldring, M.B. and S.R. Goldring, Osteoarthritis. J Cell Physiol, 2007. 213(3): p. 626-34. 13. Dudhia, J., Aggrecan, aging and assembly in articular cartilage. Cell Mol Life Sci, 2005. 62(19-20): p. 2241-56. 14. Loeser, R.F., Molecular mechanisms of cartilage destruction: mechanics, inflammatory mediators, and aging collide. Arthritis Rheum, 2006. 54(5): p. 1357-60. 15. Aigner, T., et al., Osteoarthritis: aging of matrix and cells--going for a remedy. Curr Drug Targets, 2007. 8(2): p. 325-31. 15 16. Martin, J.A., et al., Chondrocyte senescence, joint loading and osteoarthritis. Clin Orthop Relat Res, 2004(427 Suppl): p. S96-103. 17. Horton, W.E., Jr., et al., Overview of studies comparing human normal cartilage with minimal and advanced osteoarthritic cartilage. Clin Exp Rheumatol, 2005. 23(1): p. 103-12. 18. Yang, L., et al., Multiple signals induce endoplasmic reticulum stress in both primary and immortalized chondrocytes resulting in loss of differentiation, impaired cell growth, and apoptosis. J Biol Chem, 2005. 280(35): p. 31156-65. 19. Keuttner, K., Goldberg, V.M.(ed.), Rosemont:American Academy of Orthopedic Surgeons. Osteoarthritic Disorders. 1995. xxi-v. 20. Redler, I., et al., The ultrastructure and biomechanical significance of the tidemark of articular cartilage. Clin Orthop Relat Res, 1975(112): p. 357-62. 21. Mente, P.L. and J.L. Lewis, Elastic modulus of calcified cartilage is an order of magnitude less than that of subchondral bone. J Orthop Res, 1994. 12(5): p. 637-47. 22. Durr, H.D., et al., The cause of subchondral bone cysts in osteoarthrosis: a finite element analysis. Acta Orthop Scand, 2004. 75(5): p. 554-8. 23. Kamibayashi, L., et al., Trabecular microstructure in the medial condyle of the proximal tibia of patients with knee osteoarthritis. Bone, 1995. 17(1): p. 27-35. 24. Milz, S. and R. Putz, Quantitative morphology of the subchondral plate of the tibial plateau. J Anat, 1994. 185 ( Pt 1): p. 103-10. 25. Lane, L.B., A. Villacin, and P.G. Bullough, The vascularity and remodelling of subchondrial bone and calcified cartilage in adult human femoral and humeral heads. An age- and stress-related phenomenon. J Bone Joint Surg Br, 1977. 59(3): p. 272-8. 26. Schett, G., Review: Immune cells and mediators of inflammatory arthritis. Autoimmunity, 2008. 41(3): p. 224-9. 27. Bleasel, J.F., et al., Type II procollagen gene (COL2A1) mutation in exon 11 associated with spondyloepiphyseal dysplasia, tall stature and precocious osteoarthritis. J Rheumatol, 1995. 22(2): p. 255-61. 28. Chan, D., T.K. Taylor, and W.G. Cole, Characterization of an arginine 789 to cysteine substitution in alpha 1 (II) collagen chains of a patient with spondyloepiphyseal dysplasia. J Biol Chem, 1993. 268(20): p. 15238-45. 29. Bogaert, R., et al., An amino acid substitution (Gly853-->Glu) in the collagen alpha 1(II) chain produces hypochondrogenesis. J Biol Chem, 1992. 267(31): p. 22522-6. 16 30. Ala-Kokko, L., et al., Single base mutation in the type II procollagen gene (COL2A1) as a cause of primary osteoarthritis associated with a mild chondrodysplasia. Proc Natl Acad Sci U S A, 1990. 87(17): p. 6565-8. 31. Boyd, L.M., et al., Early-onset degeneration of the intervertebral disc and vertebral end plate in mice deficient in type IX collagen. Arthritis Rheum, 2008. 58(1): p. 164-71. 32. Li, Y., L. Xu, and B.R. Olsen, Lessons from genetic forms of osteoarthritis for the pathogenesis of the disease. Osteoarthritis Cartilage, 2007. 15(10): p. 1101-5. 33. Valdes, A.M., et al., Reproducible genetic associations between candidate genes and clinical knee osteoarthritis in men and women. Arthritis Rheum, 2006. 54(2): p. 533-9. 34. Henrotin, Y., et al., Type II collagen markers in osteoarthritis: what do they indicate? Curr Opin Rheumatol, 2007. 19(5): p. 444-50. 35. Meulenbelt, I., et al., Strong linkage on 2q33.3 to familial early-onset generalized osteoarthritis and a consideration of two positional candidate genes. Eur J Hum Genet, 2006. 14(12): p. 1280-7. 36. Valdes, A.M., et al., Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee. Arthritis Rheu00000000000000000000000000m, 2007. 56(1): p. 137-46. 37. Van Der Hout, A.H., et al., Occurrence of deletion of a COL2A1 allele as the mutation in Stickler syndrome shows that a collagen type II dosage effect underlies this syndrome. Hum Mutat, 2002. 20(3): p. 236. 38. Prockop, D.J., Mutations that alter the primary structure of type I collagen. The perils of a system for generating large structures by the principle of nucleated growth. J Biol Chem, 1990. 265(26): p. 15349-52. 39. Stattin, E.L., et al., Familial osteochondritis dissecans associated with early osteoarthritis and disproportionate short stature. Osteoarthritis Cartilage, 2008. 40. Lopponen, T., et al., Childhood-onset osteoarthritis, tall stature, and sensorineural hearing loss associated with Arg75-Cys mutation in procollagen type II gene (COL2A1). Arthritis Rheum, 2004. 51(6): p. 925-32. 41. Loughlin, J., Polymorphism in signal transduction is a major route through which osteoarthritis susceptibility is acting. Curr Opin Rheumatol, 2005. 17(5): p. 629-33. 42. Bukulmez, H., et al., Hip joint replacement surgery for idiopathic osteoarthritis aggregates in families. Arthritis Res Ther, 2006. 8(1): p. R25. 17 43. Liu, Y.F., et al., Type II collagen gene variants and inherited osteonecrosis of the femoral head. N Engl J Med, 2005. 352(22): p. 2294-301. 44. Tsezou, A., et al., Association of KLOTHO gene polymorphisms with knee osteoarthritis in Greek population. J Orthop Res, 2008. 45. Uitterlinden, A.G., et al., Adjacent genes, for COL2A1 and the vitamin D receptor, are associated with separate features of radiographic osteoarthritis of the knee. Arthritis Rheum, 2000. 43(7): p. 1456-64. 46. Meulenbelt, I., et al., Haplotype analysis of three polymorphisms of the COL2A1 gene and associations with generalised radiological osteoarthritis. Ann Hum Genet, 1999. 63(Pt 5): p. 393-400. 47. Loughlin, J., et al., Differential allelic expression of the type II collagen gene (COL2A1) in osteoarthritic cartilage. Am J Hum Genet, 1995. 56(5): p. 1186-93. 48. Loughlin, J., et al., Sibling pair analysis shows no linkage of generalized osteoarthritis to the loci encoding type II collagen, cartilage link protein or cartilage matrix protein. Br J Rheumatol, 1994. 33(12): p. 1103-6. 49. Zeng, Q.Y., et al., Rheumatic diseases in China. Arthritis Res Ther, 2008. 10(1): p. R17. 50. Nejentsev, S., et al., Comparative high-resolution analysis of linkage disequilibrium and tag single nucleotide polymorphisms between populations in the vitamin D receptor gene. Hum Mol Genet, 2004. 13(15): p. 1633-9. 51. Loughlin, J., et al., Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Proc Natl Acad Sci U S A, 2004. 101(26): p. 9757-62. 52. Sahlman, J., et al., Premature vertebral endplate ossification and mild disc degeneration in mice after inactivation of one allele belonging to the Col2a1 gene for Type II collagen. Spine, 2001. 26(23): p. 2558-65. 53. Sarver, J.J. and D.M. Elliott, Altered disc mechanics in mice genetically engineered for reduced type I collagen. Spine, 2004. 29(10): p. 1094-8. 54. Kizawa, H., et al., An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis. Nat Genet, 2005. 37(2): p. 138-44. 55. Mustafa, Z., et al., Investigating the aspartic acid (D) repeat of asporin as a risk factor for osteoarthritis in a UK Caucasian population. Arthritis Rheum, 2005. 52(11): p. 3502-6. 56. Meulenbelt, I., et al., Identification of DIO2 as a new susceptibility locus for symptomatic osteoarthritis. Hum Mol Genet, 2008. 17(12): p. 1867-75. 57. Mabuchi, A., et al., Identification of sequence polymorphisms of the COMP 18 (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints. J Hum Genet, 2001. 46(8): p. 456-62. 58. Mototani, H., et al., A functional single nucleotide polymorphism in the core promoter region of CALM1 is associated with hip osteoarthritis in Japanese. Hum Mol Genet, 2005. 14(8): p. 1009-17. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37357 | - |
| dc.description.abstract | 骨關節炎是一種常見關節發生退化的病變，好發於手、膝蓋、髖關節以及脊椎等處，發病後會導致行動不便以及疼痛因而嚴重影響生活品質。除了年齡或是物理性傷害之外，遺傳因子的變異也是造成骨關節炎的一個重要因素。根據之前的研究報導指出，軟骨生成及代謝相關的基因若發生突變，往往會提高骨關節炎發生的機率，帶有這些基因變異的家族常常會有早發性骨關節炎的發生。因此，針對這些與骨關節炎相關的基因建立基因診斷的方法，對於預防骨關節炎的發生是非常重要的，尤其是有家族性早發性骨關節炎病史的家族。本實驗室之前的研究中發現，第二型膠原蛋白的基因發生突變(3689GÎA)與家族性早發性骨關節炎之間有著顯著的關係。本次實驗收集一個早發性骨關節炎家族的檢體進行實驗，共十一位家屬，利用不同引子進行聚合酶鏈鎖反應，將檢體裡COL2A1 基因的部分片段放大，再加以定序。比對結果後發現，在exon34、exon37、exon40以及exon53 等處發現有異合子的現象，分別是SNP ID:rs2276454、rs1635553、rs41272029 以及rs2070739。其中exon53 處所發現之SNPrs2070739)G->A 則會造成蛋白質序列上的變化，由甘胺酸(glycine)變成絲胺酸(serine)。然而，exon53處所發現之SNP 雖然會造成蛋白質序列上的改變，但是經過族譜比對之後與家族性骨關節炎並沒有關聯。相關文獻以及資料中提及，此SNP 在華人的族群裡出現比率偏高，約是六比四，而高加索人的族群裡則是一比九的比例。因此，我們認為此SNP 與此次實驗中遺傳性家族性骨關節炎並沒有相關。根據本研究結果顯示，在台灣地區除了之前報導的第二型膠原蛋白基因發生突變會引發早發性骨關節炎外，或許還有其他的基因變異參與其中，未來值得做更進一步的探討。 | zh_TW |
| dc.description.abstract | Osteoarthritis (OA) is a common type of degenerative arthritis, and it usually concerns hands, knees, hips, and spines, leading to the difficulty in movement, pain, and thus poor quality of life. In addition to aging and physical injuries, genetic susceptibility is also considered an important cause of OA. According to previous
studies, mutations in the related genes of cartilage commonly increase the probability of OA. The families with these mutated genes also have a higher incidence of early onset OA. As a result, it is very important to establish the method for genetic diagnosis of OA-related to prevent its occurrence, especially for those families in high risk. Previously in our laboratory, we found a mutation of type II collagen (3689GÎA) in a family of early onset OA. In this study, eleven subjects belonging to another victim family of early onset OA were investigated for COL2A1 mutation by PCR-sequencing. After comparison, heterozygotes are found in exon34, exon37, exon40, and exon53 (SNP ID:rs2276454, rs1635553, rs41272029, and rs2070739 respectively). Among these heterozygotes, SNP (rs2070739) G->A, which was found in exon53, results in amino acid change from glycine to serine. However, this mutation does not co-segregate with the phenotype of OA. Moreover, this SNP in exon54 is found commonly in Chinese ethnicity (about 4:6). It is concluded that this SNP (rs2070739) has no relation to familial OA in this study. In conclusion, genes other than COL2A1 may be responsible for familial early-onset OA in this specific family. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T15:25:26Z (GMT). No. of bitstreams: 1 ntu-97-P95448001-1.pdf: 2313772 bytes, checksum: 151a32bb2a4bf2d6967976a4f64a1452 (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 口試委員會審定書 Ⅰ
謝辭 Ⅱ 中文摘要 Ⅲ 英文摘要 Ⅳ 第一章 前言 1 1.1 骨關節炎 1 1.2 關節的結構 1 1.2.1 膠原蛋白 2 1.2.2 蛋白多醣 2 1.2.3 軟骨細胞 2 1.3 骨關節炎的發生 2 1.4 骨關節炎的病理機轉 3 1.4.1軟骨組織的病理機轉 3 1.4.2骨頭組織的病理機轉 3 1.4.3滑液膜組織的病理機轉 4 1.5 骨關節炎之遺傳因素 4 1.6 家族性早發性骨關節炎 5 第二章 材料與方法 6 2.1 檢體 6 2.2 DNA 的萃取 6 2.3 聚合酶鏈鎖反應(PCR) 7 2.4 挖膠純化(Purification) 7 2.5 定序反應(Sequencing) 8 2.6 結果判讀 8 第三章 結果 10 第四章 討論 11 參考文獻 14 圖表 19 | |
| dc.language.iso | zh-TW | |
| dc.subject | 第二型膠原 | zh_TW |
| dc.subject | 家族遺傳 | zh_TW |
| dc.subject | 骨關節炎 | zh_TW |
| dc.subject | osteoarthritis | en |
| dc.subject | familial heredity | en |
| dc.subject | type II collagen | en |
| dc.title | 家族性早發性骨關節炎的遺傳診斷與諮詢II | zh_TW |
| dc.title | Familial Early-Onset Osteoarthritis：Genetic Diagnosis and
Counseling II | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 江清泉(Ching-Chuan Chiang) | |
| dc.contributor.oralexamcommittee | 蘇怡寧 | |
| dc.subject.keyword | 骨關節炎,第二型膠原,家族遺傳, | zh_TW |
| dc.subject.keyword | osteoarthritis,type II collagen,familial heredity, | en |
| dc.relation.page | 36 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2008-07-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-97-1.pdf 未授權公開取用 | 2.26 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。