New molecular targets for the treatment of osteoarthritis

Biochemical Pharmacology

Volumn 80, Issue 1, 2010, Pages 13-21

  Alcaraz, Maria José ^a   Megías, Javier ^a   García Arnandis, Isabel ^a   Clérigues, Victoria ^a   Guillén, Maria Isabel ^a  

^a UNIVERSITY OF VALENCIA   (Spain)

Author keywords

Cytokines; Growth factors; MicroRNA; Osteoarthritis; Wnt catenin

Indexed keywords

AGGRECANASE; ALS 1 0635; BETA CATENIN; BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN 4; CARBOXYLIC ACID DERIVATIVE; CYTOKINE; DISCOIDIN; GROWTH FACTOR; HYDROXAMIC ACID DERIVATIVE; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 1BETA CONVERTING ENZYME INHIBITOR; MATRIX METALLOPROTEINASE; MATRIX METALLOPROTEINASE INHIBITOR; MICRORNA; NBI 31772; PROTEINASE; PROTEINASE ACTIVATED RECEPTOR 2; REGULATOR PROTEIN; RU 36384; SC 81956; SOMATOMEDIN BINDING PROTEIN; SOMATOMEDIN C; SYNDECAN; TISSUE INHIBITOR OF METALLOPROTEINASE 3; TRANSFORMING GROWTH FACTOR BETA3; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN RECEPTOR 1; VIRUS VECTOR; WNT PROTEIN;

ANTIANGIOGENIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BONE REMODELING; CHONDROPATHY; CLINICAL TRIAL; DISEASE COURSE; DRUG DESIGN; DRUG PROTEIN BINDING; DRUG RESEARCH; DRUG TARGETING; EPIGENETICS; HUMAN; MOLECULAR MECHANICS; MUSCULOSKELETAL DISEASE; NONHUMAN; OSTEOARTHRITIS; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN METABOLISM; PROTEIN SYNTHESIS INHIBITION; SIGNAL TRANSDUCTION; SYNOVITIS; VIRAL GENE DELIVERY SYSTEM;

EID: 77952266181     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2010.02.017     Document Type: Note

References (99)

1. Goldring M.B., Goldring S.R. Osteoarthritis. J Cell Physiol 2007, 213:626-634.
2. Goldring M.B., Marcu K.B. Cartilage homeostasis in health and rheumatic diseases. Arthritis Res Ther 2009, 11:224.
3. Schmidt M.B., Chen E.H., Lynch S.E. A review of the effects of insulin-like growth factor and platelet derived growth factor on in vivo cartilage healing and repair. Osteoarthritis Cartilage 2006, 14:403-412.
4. Dore S., Pelletier J.P., DiBattista J.A., Tardif G., Brazeau P., Martel-Pelletier J. Human osteoarthritic chondrocytes possess an increased number of insulin-like growth factor 1 binding sites but are unresponsive to its stimulation. Possible role of IGF-1-binding proteins. Arthritis Rheum 1994, 37:253-263.
5. Massicotte F., Aubry I., Martel-Pelletier J., Pelletier J.P., Fernandes J., Lajeunesse D. Abnormal insulin-like growth factor 1 signaling in human osteoarthritic subchondral bone osteoblasts. Arthritis Res Ther 2006, 8:R177.
6. De Ceuninck F., Caliez A., Dassencourt L., Anract P., Renard P. Pharmacological disruption of insulin-like growth factor 1 binding to IGF-binding proteins restores anabolic responses in human osteoarthritic chondrocytes. Arthritis Res Ther 2004, 6:R393-R403.
7. Haupt J.L., Frisbie D.D., McIlwraith C.W., Robbins P.D., Ghivizzani S., Evans C.H., et al. Dual transduction of insulin-like growth factor-I and interleukin-1 receptor antagonist protein controls cartilage degradation in an osteoarthritic culture model. J Orthop Res 2005, 23:118-126.
8. Loeser R.F., Todd M.D., Seely B.L. Prolonged treatment of human osteoarthritic chondrocytes with insulin-like growth factor-I stimulates proteoglycan synthesis but not proteoglycan matrix accumulation in alginate cultures. J Rheumatol 2003, 30:1565-1570.
9. Loeser R.F., Pacione C.A., Chubinskaya S. The combination of insulin-like growth factor 1 and osteogenic protein 1 promotes increased survival of and matrix synthesis by normal and osteoarthritic human articular chondrocytes. Arthritis Rheum 2003, 48:2188-2196.
10. Goldring M.B. Are bone morphogenetic proteins effective inducers of cartilage repair? Ex vivo transduction of muscle-derived stem cells. Arthritis Rheum 2006, 54:387-389.
11. Jeon E.J., Lee K.Y., Choi N.S., Lee M.H., Kim H.N., Jin Y.H., et al. Bone morphogenetic protein-2 stimulates Runx2 acetylation. J Biol Chem 2006, 281:16502-16511.
12. Tardif G., Hum D., Pelletier J.P., Boileau C., Ranger P., Martel-Pelletier J. Differential gene expression and regulation of the bone morphogenetic protein antagonists follistatin and gremlin in normal and osteoarthritic human chondrocytes and synovial fibroblasts. Arthritis Rheum 2004, 50:2521-2530.
13. Tang Q.O., Shakib K., Heliotis M., Tsiridis E., Mantalaris A., Ripamonti U., et al. TGF-beta3: A potential biological therapy for enhancing chondrogenesis. Expert Opin Biol Ther 2009, 9:689-701.
14. Blaney Davidson E.N., Vitters E.L., van der Kraan P.M., van den Berg W.B. Expression of transforming growth factor-beta (TGFbeta) and the TGFbeta signalling molecule Smad-2P in spontaneous and instability-induced osteoarthritis: role in cartilage degradation, chondrogenesis and osteophyte formation. Ann Rheum Dis 2006, 65:1414-1421.
15. Blaney Davidson E.N., Vitters E.L., van den Berg W.B., van der Kraan P.M. TGF beta-induced cartilage repair is maintained but fibrosis is blocked in the presence of Smad7. Arthritis Res Ther 2006, 8:R65.
16. Muddasani P., Norman J.C., Ellman M., Van Wijnen A.J., Im H.J. Basic fibroblast growth factor activates the MAPK and NFkappaB pathways that converge on Elk-1 to control production of matrix metalloproteinase-13 by human adult articular chondrocytes. J Biol Chem 2007, 282:31409-31421.
17. Koelling S., Miosge N. Stem cell therapy for cartilage regeneration in osteoarthritis. Expert Opin Biol Ther 2009, 9:1399-1405.
18. Bai X., Xiao Z., Pan Y., Hu J., Pohl J., Wen J., et al. Cartilage-derived morphogenetic protein-1 promotes the differentiation of mesenchymal stem cells into chondrocytes. Biochem Biophys Res Commun 2004, 325:453-460.
19. Kubo S., Cooper G.M., Matsumoto T., Phillippi J.A., Corsi K.A., Usas A., et al. Blocking vascular endothelial growth factor with soluble Flt-1 improves the chondrogenic potential of mouse skeletal muscle-derived stem cells. Arthritis Rheum 2009, 60:155-165.
20. Matsumoto T., Cooper G.M., Gharaibeh B., Meszaros L.B., Li G., Usas A., et al. Cartilage repair in a rat model of osteoarthritis through intraarticular transplantation of muscle-derived stem cells expressing bone morphogenetic protein 4 and soluble Flt-1. Arthritis Rheum 2009, 60:1390-1405.
21. Pufe T., Petersen W., Fandrich F., Varoga D., Wruck C.J., Mentlein R., et al. Programmable cells of monocytic origin (PCMO): a source of peripheral blood stem cells that generate collagen type II-producing chondrocytes. J Orthop Res 2008, 26:304-313.
22. Li X, Wu JF. Recent developments in patent anti-cancer agents targeting the matrix metalloproteinases (MMPs). Recent Pat Anticancer Drug Discov 2009 [Epub ahead of print].
23. Little C.B., Barai A., Burkhardt D., Smith S.M., Fosang A.J., Werb Z., et al. Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum 2009, 60:3723-3733.
24. Gooljarsingh L.T., Lakdawala A., Coppo F., Luo L., Fields G.B., Tummino P.J., et al. Characterization of an exosite binding inhibitor of matrix metalloproteinase 13. Protein Sci 2008, 17:66-71.
25. Monovich L.G., Tommasi R.A., Fujimoto R.A., Blancuzzi V., Clark K., Cornell W.D., et al. Discovery of potent, selective, and orally active carboxylic acid based inhibitors of matrix metalloproteinase-13. J Med Chem 2009, 52:3523-3538.
26. Baragi V.M., Becher G., Bendele A.M., Biesinger R., Bluhm H., Boer J., et al. A new class of potent matrix metalloproteinase 13 inhibitors for potential treatment of osteoarthritis: Evidence of histologic and clinical efficacy without musculoskeletal toxicity in rat models. Arthritis Rheum 2009, 60:2008-2018.
27. Johnson A.R., Pavlovsky A.G., Ortwine D.F., Prior F., Man C.F., Bornemeier D.A., et al. Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia side effects. J Biol Chem 2007, 282:27781-27791.
28. Kashiwagi M., Tortorella M., Nagase H., Brew K. TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2 (ADAM-TS5). J Biol Chem 2001, 276:12501-12504.
29. Zhao H., Bernardo M.M., Osenkowski P., Sohail A., Pei D., Nagase H., et al. Differential inhibition of membrane type 3 (MT3)-matrix metalloproteinase (MMP) and MT1-MMP by tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-3 regulates pro-MMP-2 activation. J Biol Chem 2004, 279:8592-8601.
30. Sahebjam S., Khokha R., Mort J.S. Increased collagen and aggrecan degradation with age in the joints of Timp3(-/-) mice. Arthritis Rheum 2007, 56:905-909.
31. Fosang A.J., Little C.B. Drug insight: aggrecanases as therapeutic targets for osteoarthritis. Nat Clin Pract Rheumatol 2008, 4:420-427.
32. Botter S.M., Glasson S.S., Hopkins B., Clockaerts S., Weinans H., Van Leeuwen J.P., et al. ADAMTS5-/- mice have less subchondral bone changes after induction of osteoarthritis through surgical instability: implications for a link between cartilage and subchondral bone changes. Osteoarthritis Cartilage 2009, 17:636-645.
33. Gilbert A.M., Bursavich M.G., Lombardi S., Georgiadis K.E., Reifenberg E., Flannery C.R., et al. 5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5. Bioorg Med Chem Lett 2007, 17:1189-1192.
34. Bursavich M.G., Gilbert A.M., Lombardi S., Georgiadis K.E., Reifenberg E., Flannery C.R., et al. Synthesis and evaluation of aryl thioxothiazolidinone inhibitors of ADAMTS-5 (Aggrecanase-2). Bioorg Med Chem Lett 2007, 17:1185-1188.
35. Bursavich M.G., Gilbert A.M., Lombardi S., Georgiadis K.E., Reifenberg E., Flannery C.R., et al. 5′-Phenyl-3′H-spiro[indoline-3,2′-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (aggrecanase-2). Bioorg Med Chem Lett 2007, 17:5630-5633.
36. Gilbert A.M., Bursavich M.G., Lombardi S., Georgiadis K.E., Reifenberg E., Flannery C.R., et al. N-((8-hydroxy-5-substituted-quinolin-7-yl)(phenyl)methyl)-2-phenyloxy/amino-acetamide inhibitors of ADAMTS-5 (Aggrecanase-2). Bioorg Med Chem Lett 2008, 18:6454-6457.
37. Wittwer A.J., Hills R.L., Keith R.H., Munie G.E., Arner E.C., Anglin C.P., et al. Substrate-dependent inhibition kinetics of an active site-directed inhibitor of ADAMTS-4 (Aggrecanase 1). Biochemistry 2007, 46:6393-6401.
38. Tortorella M.D., Tomasselli A.G., Mathis K.J., Schnute M.E., Woodard S.S., Munie G., et al. Structural and inhibition analysis reveals the mechanism of selectivity of a series of aggrecanase inhibitors. J Biol Chem 2009, 284:24185-24191.
39. Troeberg L., Fushimi K., Khokha R., Emonard H., Ghosh P., Nagase H. Calcium pentosan polysulfate is a multifaceted exosite inhibitor of aggrecanases. FASEB J 2008, 22:3515-3524.
40. Kizawa H., Kou I., Iida A., Sudo A., Miyamoto Y., Fukuda A., et al. An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis. Nat Genet 2005, 37:138-144.
41. Sakao K., Takahashi K.A., Arai Y., Saito M., Honjyo K., Hiraoka N., et al. Asporin and transforming growth factor-beta gene expression in osteoblasts from subchondral bone and osteophytes in osteoarthritis. J Orthop Sci 2009, 14:738-747.
42. Bartlett A.H., Hayashida K., Park P.W. Molecular and cellular mechanisms of syndecans in tissue injury and inflammation. Mol Cells 2007, 24:153-166.
43. Echtermeyer F., Bertrand J., Dreier R., Meinecke I., Neugebauer K., Fuerst M., et al. Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis. Nat Med 2009, 15:1072-1076.
44. Klatt A.R., Zech D., Kuhn G., Paul-Klausch B., Klinger G., Renno J.H., et al. Discoidin domain receptor 2 mediates the collagen II-dependent release of interleukin-6 in primary human chondrocytes. J Pathol 2009, 218:241-247.
45. Boileau C., Amiable N., Martel-Pelletier J., Fahmi H., Duval N., Pelletier J.P. Activation of proteinase-activated receptor 2 in human osteoarthritic cartilage upregulates catabolic and proinflammatory pathways capable of inducing cartilage degradation: a basic science study. Arthritis Res Ther 2007, 9:R121.
46. Amiable N., Tat S.K., Lajeunesse D., Duval N., Pelletier J.P., Martel-Pelletier J., et al. Proteinase-activated receptor (PAR)-2 activation impacts bone resorptive properties of human osteoarthritic subchondral bone osteoblasts. Bone 2009, 44:1143-1150.
47. Fernandes J.C., Martel-Pelletier J., Pelletier J.P. The role of cytokines in osteoarthritis pathophysiology. Biorheology 2003, 39:237-246.
48. Rudolphi K., Gerwin N., Verzijl N., van der K.P., van den B.W. Pralnacasan, an inhibitor of interleukin-1beta converting enzyme, reduces joint damage in two murine models of osteoarthritis. Osteoarthritis Cartilage 2003, 11:738-746.
49. Caron J.P., Fernandes J.C., Martel-Pelletier J., Tardif G., Mineau F., Geng C., et al. Chondroprotective effect of intraarticular injections of interleukin-1 receptor antagonist in experimental osteoarthritis. Suppression of collagenase-1 expression. Arthritis Rheum 1996, 39:1535-1544.
50. Evans C.H., Gouze J.N., Gouze E., Robbins P.D., Ghivizzani S.C. Osteoarthritis gene therapy. Gene Ther 2004, 11:379-389.
51. Evans C.H. Novel biological approaches to the intra-articular treatment of osteoarthritis. BioDrugs 2005, 19:355-362.
52. Tat S.K., Pelletier J.P., Velasco C.R., Padrines M., Martel-Pelletier J. New perspective in osteoarthritis: the OPG and RANKL system as a potential therapeutic target?. Keio J Med 2009, 58:29-40.
53. Shimizu S., Asou Y., Itoh S., Chung U.I., Kawaguchi H., Shinomiya K., et al. Prevention of cartilage destruction with intraarticular osteoclastogenesis inhibitory factor/osteoprotegerin in a murine model of osteoarthritis. Arthritis Rheum 2007, 56:3358-3365.
54. Kwan T.S., Amiable N., Pelletier J.P., Boileau C., Lajeunesse D., Duval N., et al. Modulation of OPG. RANK and RANKL by human chondrocytes and their implication during osteoarthritis. Rheumatology (Oxford) 2009, 48:1482-1490.
55. Kwan T.S., Pelletier J.P., Amiable N., Boileau C., Lajeunesse D., Duval N., et al. Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts. Arthritis Rheum 2008, 58:3820-3830.
56. Yorimitsu M., Nishida K., Shimizu A., Doi H., Miyazawa S., Komiyama T., et al. Intra-articular injection of interleukin-4 decreases nitric oxide production by chondrocytes and ameliorates subsequent destruction of cartilage in instability-induced osteoarthritis in rat knee joints. Osteoarthritis Cartilage 2008, 16:764-771.
57. El Mabrouk M., Qureshi H.Y., Li W.Q., Sylvester J., Zafarullah M. Interleukin-4 antagonizes oncostatin M and transforming growth factor beta-induced responses in articular chondrocytes. J Cell Biochem 2008, 103:588-597.
58. Carlo M.D., Loeser R.F. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum 2003, 48:3419-3430.
59. Studer R.K., Levicoff E., Georgescu H., Miller L., Jaffurs D., Evans C.H. Nitric oxide inhibits chondrocyte response to IGF-I: inhibition of IGF-IRbeta tyrosine phosphorylation. Am J Physiol Cell Physiol 2000, 279:C961-C969.
60. Grishko V., Xu M., Ho R., Mates A., Watson S., Kim J.T., et al. Effects of hyaluronic acid on mitochondrial function and mitochondria-driven apoptosis following oxidative stress in human chondrocytes. J Biol Chem 2009, 284:9132-9139.
61. Aigner T., Fundel K., Saas J., Gebhard P.M., Haag J., Weiss T., et al. Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis. Arthritis Rheum 2006, 54:3533-3544.
62. Wang M.X., Wei A., Yuan J., Trickett A., Knoops B., Murrell G.A. Expression and regulation of peroxiredoxin 5 in human osteoarthritis. FEBS Lett 2002, 531:359-362.
63. Yudoh K., Shishido K., Murayama H., Yano M., Matsubayashi K., Takada H., et al. Water-soluble C60 fullerene prevents degeneration of articular cartilage in osteoarthritis via down-regulation of chondrocyte catabolic activity and inhibition of cartilage degeneration during disease development. Arthritis Rheum 2007, 56:3307-3318.
64. Semenza G.L., Agani F., Booth G., Forsythe J., Iyer N., Jiang B.H., et al. Structural and functional analysis of hypoxia-inducible factor 1. Kidney Int 1997, 51:553-555.
65. Duval E., Leclercq S., Elissalde J.M., Demoor M., Galera P., Boumediene K. Hypoxia-inducible factor 1alpha inhibits the fibroblast-like markers type I and type III collagen during hypoxia-induced chondrocyte redifferentiation: hypoxia not only induces type II collagen and aggrecan, but it also inhibits type I and type III collagen in the hypoxia-inducible factor 1alpha-dependent redifferentiation of chondrocytes. Arthritis Rheum 2009, 60:3038-3048.
66. Yudoh K., Nakamura H., Masuko-Hongo K., Kato T., Nishioka K. Catabolic stress induces expression of hypoxia-inducible factor (HIF)-1alpha in articular chondrocytes: involvement of HIF-1alpha in the pathogenesis of osteoarthritis. Arthritis Res Ther 2005, 7:R904-R914.
67. Wan C., Gilbert S.R., Wang Y., Cao X., Shen X., Ramaswamy G., et al. Activation of the hypoxia-inducible factor-1alpha pathway accelerates bone regeneration. Proc Natl Acad Sci USA 2008, 105:686-691.
68. Alcaraz M.J., Fernandez P., Guillen M.I. Anti-inflammatory actions of the heme oxygenase-1 pathway. Curr Pharm Des 2003, 9:2541-2551.
69. Fernandez P., Guillen M.I., Gomar F., Alcaraz M.J. Expression of heme oxygenase-1 and regulation by cytokines in human osteoarthritic chondrocytes. Biochem Pharmacol 2003, 66:2049-2052.
70. Guillen M.I., Megias J., Gomar F., Alcaraz M.J. Heme oxygenase-1 regulates catabolic and anabolic processes in osteoarthritic chondrocytes. J Pathol 2008, 214:515-522.
71. Megias J., Guillen M.I., Bru A., Gomar F., Alcaraz M.J. The CO-releasing molecule CORM-2 protects human osteoarthritic chondrocytes and cartilage from the catabolic actions of interleukin-1. J Pharmacol Exp Ther 2008, 325:56-61.
72. Guillen M.I., Megias J., Clerigues V., Gomar F., Alcaraz M.J. The CO-releasing molecule CORM-2 is a novel regulator of the inflammatory process in osteoarthritic chondrocytes. Rheumatology (Oxford) 2008, 47:1323-1328.
73. Megias J., Guillen M.I., Clerigues V., Rojo A.I., Cuadrado A., Castejon M.A., et al. Heme oxygenase-1 induction modulates microsomal prostaglandin E synthase-1 expression and prostaglandin E(2) production in osteoarthritic chondrocytes. Biochem Pharmacol 2009, 77:1806-1813.
74. Sondergaard B.C., Schultz N., Madsen S.H., Bay-Jensen A.C., Kassem M., Karsdal M.A. MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation - divergence in pathways leading to aggrecanase and MMP-mediated articular cartilage degradation. Osteoarthritis Cartilage 2010, 18:279-288.
75. Brown K.K., Heitmeyer S.A., Hookfin E.B., Hsieh L., Buchalova M., Taiwo Y.O., et al. P38 MAP kinase inhibitors as potential therapeutics for the treatment of joint degeneration and pain associated with osteoarthritis. J Inflamm (Lond) 2008, 5:22.
76. Amos N., Lauder S., Evans A., Feldmann M., Bondeson J. Adenoviral gene transfer into osteoarthritis synovial cells using the endogenous inhibitor IkappaBalpha reveals that most, but not all, inflammatory and destructive mediators are NFkappaB dependent. Rheumatology (Oxford) 2006, 45:1201-1209.
77. Chen L.X., Lin L., Wang H.J., Wei X.L., Fu X., Zhang J.Y., et al. Suppression of early experimental osteoarthritis by in vivo delivery of the adenoviral vector-mediated NF-kappaBp65-specific siRNA. Osteoarthritis Cartilage 2008, 16:174-184.
78. Lauder S.N., Carty S.M., Carpenter C.E., Hill R.J., Talamas F., Bondeson J., et al. Interleukin-1beta induced activation of nuclear factor-kappaB can be inhibited by novel pharmacological agents in osteoarthritis. Rheumatology (Oxford) 2007, 46:752-758.
79. Lodewyckx L., Lories R.J. WNT Signaling in osteoarthritis and osteoporosis: what is the biological significance for the clinician?. Curr Rheumatol Rep 2009, 11:23-30.
80. Shortkroff S., Yates K.E. Alteration of matrix glycosaminoglycans diminishes articular chondrocytes' response to a canonical Wnt signal. Osteoarthritis Cartilage 2007, 15:147-154.
81. Dell'Accio F., De Bari C., Eltawil N.M., Vanhummelen P., Pitzalis C. Identification of the molecular response of articular cartilage to injury by microarray screening: Wnt-16 expression and signaling after injury and in osteoarthritis. Arthritis Rheum 2008, 58:1410-1421.
82. Blom A.B., Brockbank S.M., van Lent P.L., van Beuningen H.M., Geurts J., Takahashi N., et al. Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum 2009, 60:501-512.
83. Taniguchi N., Carames B., Kawakami Y., Amendt B.A., Komiya S., Lotz M. Chromatin protein HMGB2 regulates articular cartilage surface maintenance via beta-catenin pathway. Proc Natl Acad Sci USA 2009, 106:16817-16822.
84. Lories R.J., Peeters J., Bakker A., Tylzanowski P., Derese I., Schrooten J., et al. Articular cartilage and biomechanical properties of the long bones in Frzb-knockout mice. Arthritis Rheum 2007, 56:4095-4103.
85. Lane N.E., Nevitt M.C., Lui L.Y., de Leon P., Corr M. Wnt signaling antagonists are potential prognostic biomarkers for the progression of radiographic hip osteoarthritis in elderly Caucasian women. Arthritis Rheum 2007, 56:3319-3325.
86. Diarra D., Stolina M., Polzer K., Zwerina J., Ominsky M.S., Dwyer D., et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med 2007, 13:156-163.
87. Zhu M., Chen M., Zuscik M., Wu Q., Wang Y.J., Rosier R.N., et al. Inhibition of beta-catenin signaling in articular chondrocytes results in articular cartilage destruction. Arthritis Rheum 2008, 58:2053-2064.
88. Huang S.M., Mishina Y.M., Liu S., Cheung A., Stegmeier F., Michaud G.A., et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 2009, 461:614-620.
89. Gilbert A.M., Bursavich M.G., Alon N., Bhat B.M., Bex F.J., Cain M., et al. Hit to lead studies on (hetero)arylpyrimidines-Agonists of the canonical Wnt-beta-catenin cellular messaging system. Bioorg Med Chem Lett 2010, 20:366-370.
90. Pelletier J.C., Lundquist J.T., Gilbert A.M., Alon N., Bex F.J., Bhat B.M., et al. (1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: a wingless beta-catenin agonist that increases bone formation rate. J Med Chem 2009, 52:6962-6965.
91. Kamekura S., Kawasaki Y., Hoshi K., Shimoaka T., Chikuda H., Maruyama Z., et al. Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability. Arthritis Rheum 2006, 54:2462-2470.
92. Lin A.C., Seeto B.L., Bartoszko J.M., Khoury M.A., Whetstone H., Ho L., et al. Modulating hedgehog signaling can attenuate the severity of osteoarthritis. Nat Med 2009, 15:1421-1425.
93. Roach H.I., Aigner T. DNA methylation in osteoarthritic chondrocytes: a new molecular target. Osteoarthritis Cartilage 2007, 15:128-137.
94. da Silva M.A., Yamada N., Clarke N.M., Roach H.I. Cellular and epigenetic features of a young healthy and a young osteoarthritic cartilage compared with aged control and OA cartilage. J Orthop Res 2009, 27:593-601.
95. Roach H.I., Yamada N., Cheung K.S., Tilley S., Clarke N.M., Oreffo R.O., et al. Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions. Arthritis Rheum 2005, 52:3110-3124.
96. Iliopoulos D., Malizos K.N., Tsezou A. Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic chondrocytes: possible molecular target for osteoarthritis therapeutic intervention. Ann Rheum Dis 2007, 66:1616-1621.
97. Wang X., Song Y., Jacobi J.L., Tuan R.S. Inhibition of histone deacetylases antagonized FGF-2 and IL-1beta effects on MMP expression in human articular chondrocytes. Growth Factors 2009, 27:40-49.
98. Tardif G., Hum D., Pelletier J.P., Duval N., Martel-Pelletier J. Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytes. BMC Musculoskelet Disord 2009, 10:148.
99. Iliopoulos D., Malizos K.N., Oikonomou P., Tsezou A. Integrative microRNA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks. PLoS ONE 2008, 3:e3740.