Genomics of osteoarthritis

Current Opinion in Rheumatology

Volumn 15, Issue 5, 2003, Pages 634-640

  Aigner, Thomas ^a   Dudhia, Jayesh ^b  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^b ROYAL VETERINARY COLLEGE   (United Kingdom)

Author keywords

Bioinformatics; Cartilage; Chondrocytes; Gene expression; Genetic defects

Indexed keywords

BETA 2 MICROGLOBULIN; CHITINASE; CLUSTERIN; COMPLEMENTARY DNA;

CARTILAGE CELL; CELL DIFFERENTIATION; DISEASE COURSE; DNA MICROARRAY; DRUG ACTIVITY; GENE EXPRESSION; GENE LOCUS; GENETIC POLYMORPHISM; GENETIC SUSCEPTIBILITY; GENOMICS; HUMAN; MESENCHYME; OSTEOARTHRITIS; PHENOTYPE; PRIORITY JOURNAL; REVIEW;

CARTILAGE, ARTICULAR; CELLS, CULTURED; CHONDROCYTES; GENE EXPRESSION; GENETIC PREDISPOSITION TO DISEASE; GENOMICS; HUMANS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; OSTEOARTHRITIS;

EID: 0041828559     PISSN: 10408711     EISSN: None     Source Type: Journal    
DOI: 10.1097/00002281-200309000-00019     Document Type: Review

References (66)

1. Loughlin J: Genetic epidemiology of primary osteoarthritis. Curr Opin Rheumatol 2001, 13:111-116.
2. Demissie S, Cupples LA, Myers R, et al.: Genome scan for quantity of hand osteoarthritis: The Framingham study. Arthritis Rheum 2002, 46:946-952.
3. Mustafa Z, Chapman K, Irven G, et al.: Linkage analysis of candidate genes as susceptibility loci for osteoarthritis-suggestive linkage of COL9A1 to female hip osteoarthritis. Rheumatology 2000, 39:299-306.
4. Ingvarsson T, Stefansson SE, Gulcher JR, et al.: A large Icelandic family with early osteoarthritis of the hip associated with a susceptibility locus on chromosome 16p. Arthritis Rheum 2001, 44:2548-2555.
5. Loughlin J, Dowling B, Mustafa Z, et al.: Refined linkage mapping of a hip osteoarthritis susceptibility locus on chromosome 2q. Rheumatology 2002, 41:955-956. Confirms absence of linkage of nodal CA to chromosome 2 regions for hip OA.
6. Gillaspy E, Spreckley K, Wallis G, et al.: Investigation of linkage on chromosome 2q and hand and knee osteoarthritis. Arthritis Rheum 2002, 46:3386-3387.
7. Stankovich J, Sale MM, Cooley HM, et al.: Investigation of chromosome 2q in osteoarthritis of the hand: no significant linkage in a Tasmanian population. Ann Rheum Dis 2002, 61:1081-1084.
8. Chapman K, Mustafa Z, Dowling B, et al.: Finer linkage mapping of primary hip osteoarthritis susceptibility on chromosome 11q in a cohort of affected female sibling pairs. Arthritis Rheum 2002, 46:1780-1783.
9. Livshits G, Kalichman L, Cohen Z, et al.: Mode of inheritance of hand osteoarthritis in ethnically homogeneous pedigrees. Hum Biol 2002, 74:849-860.
10. Jonsson H, Manolescu I, Stefansson SE, et al.: The inheritance of hand osteoarthritis in Iceland. Arthritis Rheum 2003, 48:391-395.
11. Crubezy E, Goulet J, Bruzek J, et al.: Epidemiology of osteoarthritis and enthesopathies in a European population dating back 7700 years. Joint Bone Spine 2002, 69:580-588.
12. Yoshida S, Aoyagi K, Felson DT, et al.: Comparison of the prevalence of radiographic osteoarthritis of the knee and hand between Japan and the United States. J Rheumatol 2002, 29:1454-1458.
13. Reginato AM, Olsen DR: The role of structural genes in the pathogenesis of osteoarthritic disorders. Arthritis Res 2002, 4:337-345. An excellent review on chondrodysplasias and on how these disorders have provided insights into the function of individual genes in the pathogenesis of OA.
14. Cohen MM Jr: Some chondrodysplaslas with short limbs: molecular perspectives. Am J Med Genet 2002, 112:304-313.
15. Fassler R, Schnegelsberg PN, Dausman J, et al.: Mice lacking alpha 1 (IX) collagen develop noninflammatory degenerative joint disease. Proc Natl Acad Sci USA 1994, 91:5070-5074.
16. Ikeda T: Mabuchi A, Fukuda A, et al: Association analysis of single nucleotide polymorphisms in cartilage-specific collagen genes with knee and hip osteoarthritis in the Japanese population. J Bone Miner Res 2002, 17:1290-1296. Reports on COL2A1 association with hip OA in a large study using SNP genotyping.
17. Loughlin J, Mustafa Z, Dowling B, et al.: Finer linkage mapping of a primary hip osteoarthritis susceptibility locus on chromosome 6. Eur J Hum Genet 2002, 10:562-568. SNP analysis to narrow the gene interval on chromosome 6 associated with hip OA that excludes the COLgA1 locus.
18. Baldwin CT, Cupples LA, Joost O, et al.: Absence of linkage or association for osteoarthritis with the vitamin D receptor/type II collagen locus: the Framingham Osteoarthritis Study. J Rheumatol 2002, 29:161-165.
19. Uitterlinden AG, Burger H, van Duijn CM, 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, 43:1456-1464.
20. Nentwich HA, Mustafa Z, Rugg MS, et al.: A novel allelic variant of the human TSG-6 gene encoding an amino acid difference in the CUB module. Chromosomal localization, frequency analysis, modeling, and expression. J Biol Chem 2002, 277:15354-15362.
21. Loughlin J, Dowling B, Mustafa Z, et al.: Association of the interleukin-1 gene cluster on chromosome 2q13 with knee osteoarthritis. Arthritis Rheum 2002, 46:1519-1527. SNP and VNTR analysis demonstrates an association of a haplotype within the interleukin 1 gene cluster on chromosome 2 in knee, but not hip OA. Differences in hip and knee OA that further highlight the genetic heterogeneity in OA are explored.
22. Kirk KM, Doege KJ, Hecht J, et al.: Osteoarthritis of the hands, hips and knees in an Australian twin sample-evidence of association with the aggrecan VNTR polymorphism. Twin Res 2003, 6:62-66.
23. Horton WE Jr, Lethbridge-Cejku M, Hochberg MC, et al.: An association between an aggrecan polymorphic allele and bilateral hand osteoarthritis in elderly white men: data from the Baltimore Longitudinal Study of Aging (BLSA). Osteoarthritis Cartilage 1998, 6:245-251.
24. Kawaguchi Y, Osada R, Kanamori M, et al.: Association between an aggrecan gene polymorphism and lumbar disc degeneration. Spine 1999, 24:2456-2460.
25. Svensson L, Aszodi A, Heinegard D, et al.: Cartilage oligomeric matrix protein-deficient mice have normal skeletal development. Mol Cell Biol 2002, 22:4366-4371. A good study that demonstrates that the disease phenotype of candidate OA genes may not appear in in vivo models.
26. Lindahl T, Satoh MS, Poirier GG, et al.: Post-translational modification of poly-(ADP-ribose) polymerase induced by DNA strand breaks. Trends Biochem Sci 1995, 20:405-411.
27. Attur MG, Dave MN, Tsunoyama K, et al.: A system biology" approach to bioinformatics and functional genomics in complex human diseases: arthritis. Curr Issues Mol Biol 2002, 4:129-146. An interesting overview of technologies involved in functional genomics of arthritis. Though not primarily related to osteoarthritis, it opens up the large field of technical possibilities, which renders the functional genomics approach potentially very powerful in future arthritis research.
28. Grant EP, Pickard MD, Briskin MJ, et al.: Gene expression profiles: creating new perspectives in arthritis research. Arthritis Rheum 2002, 46:874-884. An interesting general review on gene expression profiling in arthritis research: it covers technological aspects as well as primary and statistical data processing and indicates the main areas of application of this technology in understanding disease processes, future patient management, and pharmacological research.
29. Stokes DG, Liu G, Coimbra IB, et al: Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis. Arthritis Rheum 2002, 46:404-419. This paper presents a very interesting comparison between differentiated and dedifferentiated fetal chondrocytes in vitro. An extensive effort was made in order to get functional insights as well as to relate these expression differences to pathological conditions such as OA.
30. Aigner T, Zien A, Gehrsitz A, et al.: Anabolic and catabolic gene expression pattern analysis in normal versus osteoarthritic cartilage using complementary DNA-array technology. Arthritis Rheum 2001,44:2777-2789. This paper presented the first data set comparing normal versus early degenerated and late-stage osteoarthritic cartilage. Based on the usage of the Clontech Cancer Array nylon membranes, significant changes in many genes including those involved in cartilage anabolism and catabolism were detected.
31. Attur MG, Dave MN, Leung MY, et al.: Functional Genomic Analysis of Type II IL-1 ? Decoy Receptor: Potential for Gene Therapy in Human Arthritis and Inflammation. J Immunol 2002, 168:2001-2010.
32. Vincenti MP, Brinckerhoff CE: Early response genes induced in chondrocytes stimulated with the inflammatory cytokine interleukin-1beta. Arthritis Res 2001, 3:381-388.
33. Koshy PJT, Lundy CJ, Rowan AD, et al.: The modulation of matrix metalloproteinase and ADAM gene expression in human chondrocytes by interleukin-1 and oncostatin M. Arthritis Rheum 2002, 46:961-967.
34. Sironen RK, Karjalainen HM, Elo MA, et al.: cDNA array reveals mechanosensitive genes in chondrocytic cells under hydrostatic pressure. Biochim Biophys Acta 2002, 1591:45-54.
35. Schnabel M, Marlovits S, Eckhoff G, et al.: Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. Osteoarthritis Cartilage 2002, 10:62-70.
36. Rose CS, Malcolm S: A TWIST in development. Trends Genet 1997, 13:384-387.
37. Fuchtbauer EM: Expression of M-twist during postimplantation development of the mouse. Dev Dyn 1995, 204:316-322.
38. Winter A, Breit S, Parsch D, et al.: Cartilage-like gene expression in differentiated human stem cell spheroids: A comparison of bone marrow-derived and adipose tissue-derived stromal cells. Arthritis Rheum 2003, 48:418-429. This paper points out the potential of gene array analysis for identification of cellular phenotypes during stem cell differentiation. This approach is of major importance in the area of tissue engineering in which the achievement and the preservation of the cellular phenotype of transplanted cells are very crucial to the therapeutic outcome. The conclusion on an osteoarthritic phenotype of chondrocytic-differentiated cells demonstrates the care needed in avoiding overinterpretation of data.
39. Zhang H, Liew CC, Marshall KW: Microarray analysis reveals the involvement of beta-2 microglobulin (B2M) in human osteoarthritis. Osteoarthritis Cartilage 2002, 10:950-960. A balanced paper working from gene expression analysis to validation and some evaluation of the functional importance of a differentially expressed gene. It also documents the limitation of gene expression analysis: no conclusive picture of the implications of the differential expression can be provided currently.
40. Connor JR, Kumar S, Sathe G, et al.: Clusterin expression in adult human normal and osteoarthritic articular cartilage. Osteoarthritis Cartilage 2001, 9:727-737.
41. Steck E, Breit S, Breusch SJ, et al.: Enhanced expression of the human chitinase 3-like 2 gene (YKL-39) but not chitinase 3-like 1 gene (YKL-40) in osteoarthritic cartilage. Biochem Biophys Res Commun 2002, 299:109-115.
42. Knorr T, Obermayr F, Bartnik E, et al.: YKL-39 (chitinase 3-like protein 2), but not YKL-40 (chitinase 3-like protein 1) is up-regulated in osteoarthritic chondrocytes. Ann Rheum Dis 2003, (in press)
43. Recklies AD, White C, Ling H: The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways. Biochem J 2002, 365:119-126.
44. Aigner T, Zien A, Bartnik E, et al.: Functional Genomics of Osteoarthritis. Pharmacogenomics 2002, 3:635-650. This is a basic and rather extensive review covering the whole process of functional genomics in osteoarthritis research. It points out tools, basic options, and limitations of the gene array technology.
45. Clancy R: Nitric oxide alters chondrocyte function by disrupting cytoskeletal signaling complexes. Osteoarthritis Cartilage 1999, 7:399-400.
46. Firestein GS, Pisetsky DS: DNA microarrays: boundless technology or bound by technology? Guidelines for studies using microarray technology. Arthritis Rheum 2002, 46:859-861.
47. Aigner T, Zimmer R: The promise and limitations of DNA microarray analysis: comment on the editorial by Firestein and Pisetsky. Arthritis Rheum 2003, 48:860.
48. Aigner T, Bertling W, Stöb H, et al.: Independent expression of fibril-forming collagens I, II, and III in chondrocytes in human osteoarthritic cartilage. J Clin Invest 1993, 91:829-837.
49. Aigner T, Zhu Y, Chanksi H, et al.: Reexpression of procollagen type IIA by adult articular chondrocytes in osteoarthritis cartilage. Arthritis Rheum 1999, 42:1443-1450.
50. Von der Mark K, Frisohholz S, Aigner T, et al.: Upregulation of type X expression in osteoarthritic cartilage. Acta Orthop Scand 1995, 66:125-129.
51. Girkontaité I, Frisohholz S, Lammi P, et al.: Immunolocalization of type X collagen in normal fetal and adult osteoarthritic cartilage with monoclonal antibodies. Matrix Biol 1996, 15:231-238.
52. Aigner T, Dudhia J: Phenotypic modulation of chondrocytes as a potential therapeutic target in osteoarthritis: a hypothesis. Ann Rheum Dis 1997, 56:287-291.
53. Aigner T, Stöb H, Weseloh G, et al.: Activation of collagen type II expression in osteoarthritic and rheumatoid cartilage. Virchows Arch B Cell Pathol Incl Mol Pathol 1992, 62:337-345.
54. Lippiello L, Hall MD, Mankin HJ: Collagen synthesis in normal and osteoarthrotic human cartilage. J Clin Invest 1977, 59:593-600.
55. Bau B, Gebhard PM, Haag J, et al.: Relative messenger RNA expression profiling of collagenases and aggrecanases in human articular chondrocytes in vivo and in vitro. Arthritis Rheum 2002, 46:2648-2657.
56. Pelletier JP, Martel-Pelletier J, Howell DS, et al.: Collagenase and collagenolytic activity in human osteoarthritic cartilage. Arthritis Rheum 1983, 26-1:63-68.
57. Blanco FJ, Guttian R, Vázquez-Martul E, et al.: Osteoarthritic chondrocytes die by apoptosis. Arthritis Rheum 1998, 41:284-289.
58. Aigner T, Hemmel M, Neureiter D, et al.: Apoptotic cell death is not a wide-spread phenomenon in normal aging and osteoarthritic human articular knee cartilage: A study of proliferation, programmed cell death (apoptosis), and viability of chondrocytes in normal and osteoarthritic human knee cartilage. Arthritis Rheum 2001, 44:1304-1312.
59. Aigner T, Kim AH: Apoptosis and cellular vitality - Issues in osteoarthritic cartilage degeneration. Arthritis Rheum 2002, 46:1986-1996.
60. Reboul P, Pelletier JP, Tardif G, et al.: The new collagenase, collagenase-3, is expressed and synthesized by human chondrocytes but not by synoviocytes. J Clin Invest 1996, 97:2011-2019.
61. Wu W, Billinghurst RC, Pidoux I, et al.: Sites of collagenase cleavage and denaturation of type II collagen in aging and osteoarthritic articular cartilage and their relationship to the distribution of matrix metalloproteinase 1 and matrix metalloproteinase 13. Arthritis Rheum 2002, 46:2087-2094.
62. Johansson N, Saarialho-Kere U, Airola K, et al.: Collagenase-3 (MMP-13) is expressed by hypertrophic chondrocytes, periosteal cells, and osteoblasts during human fetal bone development. Dev Dyn 1997, 208:387-397.
63. Aigner T, Vornehm SI, Zeiler G, et al.: Suppression of cartilage matrix gene expression in upper zone chondrocytes of osteoarthritic cartilage. Arthritis Rheum 1997, 40:562-569.
64. Sandberg M, Vuorio E: Localization of types I, II, and III collagen mRNAs in developing human skeletal tissues by in situ hybridization. J Cell Biol 1987, 104:1077-1084.
65. Vornehm SI, Dudhia J, von der Mark K, et al.: Expression of collagen types IX and XI as well as other major cartilage matrix components by human fetal chondrocytes in vivo. Matrix Biol 1996, 15:91-98.
66. Gebhard PM, Gehrsitz A, Bau B, et al.: Quantification of expression levels of cellular differentiation markers does not support a general shift in the cellular phenotype of osteoarthritic chondrocytes. J Orthop Res 2003, 21:96-101.