A review of crosstalk between MAPK and Wnt signals and its impact on cartilage regeneration

Cell and Tissue Research

Volumn 358, Issue 3, 2014, Pages 633-649

  Zhang, Ying ^a,b   Pizzute, Tyler ^a   Pei, Ming ^a,b  

^a WEST VIRGINIA UNIVERSITY   (United States)

^b West Virginia University   (United States)

Author keywords

Chondrogenesis; MAPK signal; Mitogen activated protein kinase (MAPK); Osteoarthritis; Stem cell; Wnt signal

Indexed keywords

BETA CATENIN; INTERLEUKIN 1; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE KINASE 6; MITOGEN ACTIVATED PROTEIN KINASE P38; MITOGEN ACTIVATED PROTEIN KINASE P38 INHIBITOR; NERVE CELL ADHESION MOLECULE; STRESS ACTIVATED PROTEIN KINASE; WNT PROTEIN; WNT11 PROTEIN; WNT3A PROTEIN; WNT5A PROTEIN; WNT7A PROTEIN;

ADJUVANT ARTHRITIS; ARTICULAR CARTILAGE; CARTILAGE CELL; CARTILAGE DEGENERATION; CELL DIFFERENTIATION; CHONDROGENESIS; COLLAGEN-INDUCED ARTHRITIS; CYTOKINE PRODUCTION; HUMAN; JOINT DESTRUCTION; MECHANICAL STRESS; MESENCHYMAL STEM CELL; MESENCHYME CELL; NONHUMAN; OSSIFICATION; OSTEOARTHRITIS; OSTEOBLAST; PROTEIN PHOSPHORYLATION; REVIEW; RHEUMATOID ARTHRITIS; TISSUE REGENERATION; WNT SIGNALING PATHWAY; ANIMAL; BIOLOGICAL MODEL; CARTILAGE; INFLAMMATION; PATHOLOGY; PHYSIOLOGY; REGENERATION; SIGNAL TRANSDUCTION;

ANIMALS; CARTILAGE; HUMANS; INFLAMMATION; MAP KINASE SIGNALING SYSTEM; MODELS, BIOLOGICAL; REGENERATION; WNT SIGNALING PATHWAY;

EID: 84912566992     PISSN: 0302766X     EISSN: 14320878     Source Type: Journal    
DOI: 10.1007/s00441-014-2010-x     Document Type: Review

References (110)

1. Akiyama H, Lyons JP, Mori-Akiyama Y, Yang X, Zhang R, Zhang Z, Deng JM, Taketo MM, Nakamura T, Behringer RR, McCrea PD, Crombrugghe B de (2004) Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev 18:1072–1087
2. Badger AM, Griswold DE, Kapadia R, Blake S, Swift BA, Hoffman SJ, Stroup GB, Webb E, Rieman DJ, Gowen M, Boehm JC, Adams JL, Lee JC (2000) Disease-modifying activity of SB 242235, a selective inhibitor of p38 mitogen-activated protein kinase, in rat adjuvant-induced arthritis. Arthritis Rheum 43:175–183
3. Beier F, LuValle P (1999) Serum induction of the collagen X promoter requires the Raf/MEK/ERK and p38 pathways. Biochem Biophys Res Commun 262:50–54
4. Benya PD, Shaffer JD (1982) Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30:215–224
5. Bikkavilli RK, Feigin ME, Malbon CC (2008a) G alpha o mediates WNT-JNK signaling through dishevelled 1 and 3, RhoA family members, and MEKK 1 and 4 in mammalian cells. J Cell Sci 121:234–245
6. Bikkavilli RK, Feigin ME, Malbon CC (2008b) p38 mitogen-activated protein kinase regulates canonical Wnt-beta-catenin signaling by inactivation of GSK3beta. J Cell Sci 121:3598–3607
7. Bobick BE, Kulyk WM (2006) MEK-ERK signaling plays diverse roles in the regulation of facial chondrogenesis. Exp Cell Res 312:1079–1192
8. Boileau C, Martel-Pelletier J, Brunet J, Schrier D, Flory C, Boily M, Pelletier JP (2006) PD-0200347, an alpha2delta ligand of the voltage gated calcium channel, inhibits in vivo activation of the Erk1/2 pathway in osteoarthritic chondrocytes: a PKC alpha dependent effect. Ann Rheum Dis 65:573–580
9. Bradley EW, Drissi MH (2010) WNT5A regulates chondrocyte differentiation through differential use of the CaN/NFAT and IKK/NF-kappaB pathways. Mol Endocrinol 24:1581–1593
10. Bradley EW, Drissi MH (2011) Wnt5b regulates mesenchymal cell aggregation and chondrocyte differentiation through the planar cell polarity pathway. J Cell Physiol 226:1683–1693
11. Burrage PS, Mix KS, Brinckerhoff CE (2006) Matrix metalloproteinases: role in arthritis. Front Biosci 11:529–543
12. Cancedda R, Castagnola P, Cancedda FD, Dozin B, Quarto R (2000) Developmental control of chondrogenesis and osteogenesis. Int J Dev Biol 44:707–714
13. Caverzasio J, Manen D (2007) Essential role of Wnt3a-mediated activation of mitogen-activated protein kinase p38 for the stimulation of alkaline phosphatase activity and matrix mineralization in C3H10T1/2 mesenchymal cells. Endocrinology 148:5323–5330
14. Červenka I, Wolf J, Mašek J, Krejci P, Wilcox WR, Kozubík A, Schulte G, Gutkind JS, Bryja V (2011) Mitogen-activated protein kinases promote WNT/beta-catenin signaling via phosphorylation of LRP6. Mol Cell Biol 31:179–189
15. Chang SH, Oh CD, Yang MS, Kang SS, Lee YS, Sonn JK, Chun JS (1998) Protein kinase C regulates chondrogenesis of mesenchymes via mitogen-activated protein kinase signaling. J Biol Chem 273:19213–19219
16. Church VL, Francis-West P (2002) Wnt signalling during limb development. Int J Dev Biol 46:927–936
17. Clancy R, Rediske J, Koehne C, Stoyanovsky D, Amin A, Attur M, Iyama K, Abramson SB (2001) Activation of stress-activated protein kinase in osteoarthritic cartilage: evidence for nitric oxide dependence. Osteoarthritis Cartilage 9:294–299
18. Dailey L, Ambrosetti D, Mansukhani A, Basilico C (2005) Mechanisms underlying differential responses to FGF signaling. Cytokine Growth Factor Rev 16:233–247
19. Day TF, Guo X, Garrett-Beal L, Yang Y (2005) Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 8:739–750
20. Dell'accio F, De Bari C, Eltawil NM, Vanhummelen P, Pitzalis C (2008) 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 58:1410–1421
21. Dequeker J, Aerssens J, Luyten FP (2003) Osteoarthritis and osteoporosis: clinical and research evidence of inverse relationship. Aging Clin Exp Res 15:426–439
22. Ding Q, Xia W, Liu JC, Yang JY, Lee DF, Xia J, Bartholomeusz G, Li Y, Pan Y, Li Z, Bargou RC, Qin J, Lai CC, Tsai FJ, Tsai CH, Hung MC (2005) Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin. Mol Cell 19:159–170
23. Dong YF, Soung do Y, Schwarz EM, O'Keefe RJ, Drissi H (2006) Wnt induction of chondrocyte hypertrophy through the Runx2 transcription factor. J Cell Physiol 208:77–86
24. Dreier R (2010) Hypertrophic differentiation of chondrocytes in osteoarthritis: the developmental aspect of degenerative joint disorders. Arthritis Res Ther 12:216
25. Du SJ, Purcell SM, Christian JL, McGrew LL, Moon RT (1995) Identification of distinct classes and functional domains of Wnts through expression of wild-type and chimeric proteins in Xenopus embryos. Mol Cell Biol 15:2625–2634
26. Enomoto-Iwamoto M, Kitagaki J, Koyama E, Tamamura Y, Wu C, Kanatani N, Koike T, Okada H, Komori T, Yoneda T, Church V, Francis-West PH, Kurisu K, Nohno T, Pacifici M, Iwamoto M (2002) The Wnt antagonist Frzb-1 regulates chondrocyte maturation and long bone development during limb skeletogenesis. Dev Biol 251:142–156
27. Fan Z, Söder S, Oehler S, Fundel K, Aigner T (2007) Activation of interleukin-1 signaling cascades in normal and osteoarthritic articular cartilage. Am J Pathol 171:938–946
28. Fanning PJ, Emkey G, Smith RJ, Grodzinsky AJ, Szasz N, Trippel SB (2003) Mechanical regulation of mitogen-activated protein kinase signaling in articular cartilage. J Biol Chem 278:50940–50948
29. Feng GJ, Goodridge HS, Harnett MM, Wei XQ, Nikolaev AV, Higson AP, Liew FY (1999) Extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases differentially regulate the lipopolysaccharide-mediated induction of inducible nitric oxide synthase and IL-12 in macrophages: Leishmania phosphoglycans subvert macrophage IL-12 production by targeting ERK MAP kinase. J Immunol 163:6403–6412
30. Gallea S, Lallemand F, Atfi A, Rawadi G, Ramez V, Spinella-Jaegle S, Kawai S, Faucheu C, Huet L, Baron R, Roman-Roman S (2001) Activation of mitogen-activated protein kinase cascades is involved in regulation of bone morphogenetic protein-2-induced osteoblast differentiation in pluripotent C2C12 cells. Bone 28:491–498
31. Ge X, Ma X, Meng J, Zhang C, Ma K, Zhou C (2009) Role of Wnt-5A in interleukin-1beta-induced matrix metalloproteinase expression in rabbit temporomandibular joint condylar chondrocytes. Arthritis Rheum 60:2714–2722
32. Gemba T, Valbracht J, Alsalameh S, Lotz M (2002) Focal adhesion kinase and mitogen-activated protein kinases are involved in chondrocyte activation by the 29-kDa amino-terminal fibronectin fragment. J Biol Chem 277:907–911
33. Geng Y, Valbracht J, Lotz M (1996) Selective activation of the mitogen activated protein kinase subgroups c-Jun NH2 terminal kinase and p38 by IL-1 and TNF in human articular chondrocytes. J Clin Invest 98:2425–2430
34. Goodridge HS, Harnett W, Liew FY, Harnett MM (2003) Differential regulation of interleukin-12 p40 and p35 induction via Erk mitogen-activated protein kinase-dependent and -independent mechanisms and the implications for bioactive IL-12 and IL-23 responses. Immunology 109:415–425
35. Guicheux J, Lemonnier J, Ghayor C, Suzuki A, Palmer G, Caverzasio J (2003) Activation of p38 mitogen-activated protein kinase and c-Jun-NH2-terminal kinase by BMP-2 and their implication in the stimulation of osteoblastic cell differentiation. J Bone Miner Res 18:2060–2068
36. Gunnell LM, Jonason JH, Loiselle AE, Kohn A, Schwarz EM, Hilton MJ, O'Keefe RJ (2010) TAK1 regulates cartilage and joint development via the MAPK and BMP signaling pathways. J Bone Miner Res 25:1784–1797
37. Guo J, Jin J, Cooper LF (2008) Dissection of sets of genes that control the character of wnt5a-deficient mouse calvarial cells. Bone 43:961–971
38. Guo X, Day TF, Jiang X, Garrett-Beal L, Topol L, Yang Y (2004) Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation. Genes Dev 18:2404–2417
39. Han Z, Boyle DL, Aupperle KR, Bennett B, Manning AM, Firestein GS (1999) Jun N-terminal kinase in rheumatoid arthritis. J Pharmacol Exp Ther 291:124–130
40. Han Z, Boyle DL, Chang L, Bennett B, Karin M, Yang L, Manning AM, Firestein GS (2001) c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest 108:73–81
41. Hartmann C (2006) A Wnt canon orchestrating osteoblastogenesis. Trends Cell Biol 16:151–158
42. Hartmann C, Tabin CJ (2000) Dual roles of Wnt signaling during chondrogenesis in the chicken limb. Development 127:3141–3159
43. Hill TP, Später D, Taketo MM, Birchmeier W, Hartmann C (2005) Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell 8:727–738
44. Hu H, Hilton MJ, Tu X, Yu K, Ornitz DM, Long F (2005) Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132:49–60
45. Hwang SG, Yu SS, Lee SW, Chun JS (2005) Wnt-3a regulates chondrocyte differentiation via c-Jun/AP-1 pathway. FEBS Lett 579:4837–4842
46. Ishitani T, Kishida S, Hyodo-Miura J, Ueno N, Yasuda J, Waterman M, Shibuya H, Moon RT, Ninomiya-Tsuji J, Matsumoto K (2003) The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling. Mol Cell Biol 23:131–139
47. Jin EJ, Lee SY, Choi YA, Jung JC, Bang OS, Kang SS (2006a) BMP-2-enhanced chondrogenesis involves p38 MAPK-mediated down-regulation of Wnt-7a pathway. Mol Cells 22:353–359
48. Jin EJ, Park JH, Lee SY, Chun JS, Bang OS, Kang SS (2006b) Wnt-5a is involved in TGF-beta3-stimulated chondrogenic differentiation of chick wing bud mesenchymal cells. Int J Biochem Cell Biol 38:183–195
49. Johnson ML, Rajamannan N (2006) Diseases of Wnt signaling. Rev Endocr Metab Disord 7:41–49
50. Kawakami Y, Wada N, Nishimatsu SI, Ishikawa T, Noji S, Nohno T (1999) Involvement of Wnt-5a in chondrogenic pattern formation in the chick limb bud. Develop Growth Differ 41:29–40
51. Kim SJ, Im DS, Kim SH, Ryu JH, Hwang SG, Seong JK, Chun CH, Chun JS (2002) Beta-catenin regulates expression of cyclooxygenase-2 in articular chondrocytes. Biochem Biophys Res Commun 296:221–226
52. Kirsch T, Mark K von der (1992a) Remodelling of collagen types I, II and X and calcification of human fetal cartilage. Bone Miner 18:107–117
53. Korb A, Tohidast-Akrad M, Cetin E, Axmann R, Smolen J, Schett G (2006) Differential tissue expression and activation of p38 MAPK alpha, beta, gamma, and delta isoforms in rheumatoid arthritis. Arthritis Rheum 54:2745–2756
54. Krejci P, Aklian A, Kaucka M, Sevcikova E, Prochazkova J, Masek JK, Mikolka P, Pospisilova T, Spoustova T, Weis M, Paznekas WA, Wolf JH, Gutkind JS, Wilcox WR, Kozubik A, Jabs EW, Bryja V, Salazar L, Vesela I, Balek L (2012) Receptor tyrosine kinases activate canonical WNT/β-catenin signaling via MAP kinase/LRP6 pathway and direct β-catenin phosphorylation. PLoS One 7:e35826
55. Krens SF, Spaink HP, Snaar-Jagalska BE (2006) Functions of the MAPK family in vertebrate-development. FEBS Lett 580:4984–4990
56. Kumar S, Votta BJ, Rieman DJ, Badger AM, Gowen M, Lee JC (2001) IL-1- and TNF-induced bone resorption is mediated by p38 mitogen activated protein kinase. J Cell Physiol 87:294–303
57. 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 downregulates matrix metalloproteinase gene expression in articular chondrocytes. Matrix Biol 21:251–262
58. Liao G, Tao Q, Kofron M, Chen JS, Schloemer A, Davis RJ, Hsieh JC, Wylie C, Heasman J, Kuan CY (2006) Jun NH2-terminal kinase (JNK) prevents nuclear beta-catenin accumulation and regulates axis formation in Xenopus embryos. Proc Natl Acad Sci U S A 103:16313–16318
59. Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810
60. Lories RJ, Peeters J, Bakker A, Tylzanowski P, Derese I, Schrooten J, Thomas JT, Luyten FP (2007) Articular cartilage and biomechanical properties of the long bones in Frzb-knockout mice. Arthritis Rheum 56:4095–4103
61. Ma L, Wang HY (2007) Mitogen-activated protein kinase p38 regulates the Wnt/cyclic GMP/Ca2+ non-canonical pathway. J Biol Chem 282:28980–28990
62. Mark K von der, Kirsch T, Nerlich A, Kuss A, Weseloh G, Glückert K, Stöss H (1992) Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy. Arthritis Rheum 35:806–811
63. Masckauchán TN, Agalliu D, Vorontchikhina M, Ahn A, Parmalee NL, Li CM, Khoo A, Tycko B, Brown AM, Kitajewski J (2006) Wnt5a signaling induces proliferation and survival of endothelial cells in vitro and expression of MMP-1 and Tie-2. Mol Biol Cell 17:5163–5172
64. Mbalaviele G, Anderson G, Jones A, De Ciechi P, Settle S, Mnich S, Thiede M, Abu-Amer Y, Portanova J, Monahan J (2006) Inhibition of p38 mitogen-activated protein kinase prevents inflammatory bone destruction. J Pharmacol Exp Ther 317:1044–1053
65. Mclay LM, Halley F, Souness JE, McKenna J, Benning V, Birrell M, Burton B, Belvisi M, Collis A, Constan A, Foster M, Hele D, Jayyosi Z, Kelley M, Maslen C, Miller G, Ouldelhkim MC, Page K, Phipps S, Pollock K, Porter B, Ratcliffe AJ, Redford EJ, Webber S, Slater B, Thybaud V, Wilsher N (2001) The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy. Bioorg Med Chem 9:537–554
66. Medicherla S, Ma JY, Mangadu R, Jiang Y, Zhao JJ, Almirez R, Kerr I, Stebbins EG, O'Young G, Kapoun AM, Luedtke G, Chakravarty S, Dugar S, Genant HK, Protter AA (2006) A selective p38 alpha mitogen-activated protein kinase inhibitor reverses cartilage and bone destruction in mice with collagen-induced arthritis. J Pharmacol Exp Ther 318:132–141
67. Meneghini MD, Ishitani T, Carter JC, Hisamoto N, Ninomiya-Tsuji J, Thorpe CJ, Hamill DR, Matsumoto K, Bowerman B (1999) MAP kinase and Wnt pathways converge to downregulate an HMG-domain repressor in Caenorhabditis elegans. Nature 399:793–797
68. Moldovan F, Pelletier JP, Hambor J, Cloutier JM, Martel-Pelletier J (1997) Collagenase-3 (matrix metalloprotease 13) is preferentially localized in the deep layer of human arthritic cartilage in situ: in vitro mimicking effect by transforming growth factor beta. Arthritis Rheum 40:1653–1661
69. Murakami S, Kan M, McKeehan WL, Crombrugghe B de (2000) Up-regulation of the chondrogenic Sox9 gene by fibroblast growth factors is mediated by the mitogen-activated protein kinase pathway. Proc Natl Acad Sci U S A 97:1113–1118
70. Nakamura K, Shirai T, Morishita S, Uchida S, Saeki-Miura K, Makishima F (1999) p38 mitogen-activated protein kinase functionally contributes to chondrogenesis induced by growth/differentiation factor-5 in ATDC5 cells. Exp Cell Res 250:351–363
71. Nishikawa M, Myoui A, Tomita T, Takahi K, Nampei A, Yoshikawa H (2003) Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. Arthritis Rheum 48:2670–2681
72. Nurminskaya M, Linsenmayer TF (1996) Identification and characterization of up-regulated genes during chondrocyte hypertrophy. Dev Dyn 206:260–271
73. Oberlender SA, Tuan RS (1994) Expression and functional involvement of N-cadherin in embryonic limb chondrogenesis. Development 120:177–187
74. Oh CD, Chang SH, Yoon YM, Lee SJ, Lee YS, Kang SS, Chun JS (2000) Opposing role of mitogen-activated protein kinase subtypes, erk-1/2 and p38, in the regulation of chondrogenesis of mesenchymes. J Biol Chem 275:5613–5619
75. Pandur P, Läsche M, Eisenberg LM, Kühl M (2002) Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis. Nature 418:636–641
76. Pelletier JP, Fernandes JC, Brunet J, Moldovan F, Schrier D, Flory C, Martel-Pelletier J (2003) In vivo selective inhibition of mitogen-activated protein kinase kinase 1/2 in rabbit experimental osteoarthritis is associated with a reduction in the development of structural changes. Arthritis Rheum 48:1582–1593
77. Robinson JA, Chatterjee-Kishore M, Yaworsky PJ, Cullen DM, Zhao W, Li C, Kharode Y, Sauter L, Babij P, Brown EL, Hill AA, Akhter MP, Johnson ML, Recker RR, Komm BS, Bex FJ (2006) Wnt/beta-catenin signaling is a normal physiological response to mechanical loading in bone. J Biol Chem 281:31720–31728
78. Rosenzweig DH, Ou SJ, Quinn TM (2013) P38 mitogen-activated protein kinase promotes dedifferentiation of primary articular chondrocytes in monolayer culture. J Cell Mol Med 17:508–517
79. Ryu JH, Chun JS (2006) Opposing roles of WNT-5A and WNT-11 in interleukin-1beta regulation of type II collagen expression in articular chondrocytes. J Biol Chem 281:22039–22047
80. Ryu JH, Kim SJ, Kim SH, Oh CD, Hwang SG, Chun CH, Oh SH, Seong JK, Huh TL, Chun JS (2002) Regulation of the chondrocyte phenotype by beta-catenin. Development 129:5541–5550
81. Sandell LJ, Aigner T (2001) Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Res 3:107–113
82. Sawakami K, Robling AG, Ai M, Pitner ND, Liu D, Warden SJ, Li J, Maye P, Rowe DW, Duncan RL, Warman ML, Turner CH (2006) The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment. J Biol Chem 281:23698–23711
83. Schett G, Tohidast-Akrad M, Smolen JS, Schmid BJ, Steiner CW, Bitzan P, Zenz P, Redlich K, Xu Q, Steiner G (2000) Activation, differential localization, and regulation of the stress-activated protein kinases, extracellular signal-regulated kinase, c-JUN N-terminal kinase, and p38 mitogen-activated protein kinase, in synovial tissue and cells in rheumatoid arthritis. Arthritis Rheum 43:2501–2512
84. Seghatoleslami MR, Roman-Blas JA, Rainville AM, Modaressi R, Danielson KG, Tuan RS (2003) Progression of chondrogenesis in C3H10T1/2 cells is associated with prolonged and tight regulation of ERK1/2. J Cell Biochem 88:1129–1144
85. Seto H, Kamekura S, Miura T, Yamamoto A, Chikuda H, Ogata T, Hiraoka H, Oda H, Nakamura K, Kurosawa H, Chug UI, Kawaguchi H, Tanaka S (2004) Distinct roles of Smad pathways and p38 pathways in cartilage-specific gene expression in synovial fibroblasts. J Clin Invest 113:718–726
86. Shlopov BV, Gumanovskaya ML, Hasty KA (2000) Autocrine regulation of collagenase 3 (matrix metalloproteinase 13) during osteoarthritis. Arthritis Rheum 43:195–205
87. Song RH, Tortorella MD, Malfait AM, Alston JT, Yang Z, Arner EC, Griggs DW (2007) Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5. Arthritis Rheum 56:575–585
88. Stanton LA, Underhill TM, Beier F (2003) MAP kinases in chondrocyte differentiation. Dev Biol 263:165–175
89. Takada I, Mihara M, Suzawa M, Ohtake F, Kobayashi S, Igarashi M, Youn MY, Takeyama K, Nakamura T, Mezaki Y, Takezawa S, Yogiashi Y, Kitagawa H, Yamada G, Takada S, Minami Y, Shibuya H, Matsumoto K, Kato S (2007) A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-gamma transactivation. Nat Cell Biol 9:1273–1285
90. Takebe K, Nishiyama T, Hayashi S, Hashimoto S, Fujishiro T, Kanzaki N, Kawakita K, Iwasa K, Kuroda R, Kurosaka M (2011) Regulation of p38 MAPK phosphorylation inhibits chondrocyte apoptosis in response to heat stress or mechanical stress. Int J Mol Med 27:329–335
91. Tamamura Y, Otani T, Kanatani N, Koyama E, Kitagaki J, Komori T, Yamada Y, Costantini F, Wakisaka S, Pacifici M, Iwamoto M, Enomoto-Iwamoto M (2005) Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification. J Biol Chem 280:19185–19195
92. Tavella S, Raffo P, Tacchetti C, Cancedda C, Castagnola P (1994) N-CAM and N-cadherin expression during in vitro chondrogenesis. Exp Cell Res 215:354–362
93. Thalhamer T, McGrath MA, Harnett MM (2008) MAPKs and their relevance to arthritis and inflammation. Rheumatology 47:409–414
94. Thornton TM, Pedraza-Alva G, Deng B, Wood CD, Aronshtam A, Clements JL, Sabio G, Davis RJ, Matthews DE, Doble B, Rincon M (2008) Phosphorylation by p38 MAPK as an alternative pathway for GSK3beta inactivation. Science 320:667–670
95. Tibbles LA, Woodgett JR (1999) The stress-activated protein kinase pathways. Cell Mol Life Sci 55:1230–1254
96. Topol L, Jiang X, Choi H, Garrett-Beal L, Carolan PJ, Yang Y (2003) Wnt-5a inhibits the canonical wnt pathway by promoting GSK-3-independent beta-catenin degradation. J Cell Biol 162:899–908
97. Toyama T, Lee HC, Koga H, Wands JR, Kim M (2010) Noncanonical Wnt11 inhibits hepatocellular carcinoma cell proliferation and migration. Mol Cancer Res 8:254–265
98. Tufan AC, Tuan RS (2001) Wnt regulation of Limb mesenchymal chondrogenesis is accompanied by altered N-cadherin-related functions. FASEB J 15:1436–1438
99. Tufan AC, Daumer KM, DeLise AM, Tuan RS (2002) AP-1 transcription factor complex is a target of signals from both WnT-7a and N-cadherin-dependent cell-cell adhesion complex during the regulation of limb mesenchymal chondrogenesis. Exp Cell Res 273:197–203
100. Tuli R, Tuli S, Nandi S, Huang X, Manner PA, Hozack WJ, Danielson KG, Hall DJ, Tuan RS (2003) Transforming growth factor-beta-mediated chondrogenesis of human mesenchymal progenitor cells involves N-cadherin and mitogen-activated protein kinase and Wnt signaling cross-talk. J Biol Chem 278:41227–41236
101. Watanabe H, Caestecker MP de, Yamada Y (2001) Transcriptional cross-talk between Smad, ERK1/2, and p38 mitogen-activated protein kinase pathways regulates transforming growth factor-beta-induced aggrecan gene expression in chondrogenic ATDC5 cells. J Biol Chem 276:14466–14473
102. Westendorf JJ, Kahler RA, Schroeder TM (2004) Wnt signaling in osteoblasts and bone diseases. Gene 341:19–39
103. Wong GT, Gavin BJ, McMahon AP (1994) Differential transformation of mammary epithelial cells by Wnt genes. Mol Cell Biol 14:6278–6286
104. Wu X, Tu X, Joeng KS, Hilton MJ, Williams DA, Long F (2008) Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling. Cell 133:340–353
105. Xu J, Wang W, Ludeman M, Cheng K, Hayami T, Lotz JC, Kapila S (2008) Chondrogenic differentiation of human mesenchymal stem cells in three-dimensional alginate gels. Tissue Eng A 14:667–680
106. Yang Y, Topol L, Lee H, Wu J (2003) Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation. Development 130:1003–1015
107. Yuasa T, Otani T, Koike T, Iwamoto M, Enomoto-Iwamoto M (2008) Wnt/beta-catenin signaling stimulates matrix catabolic genes and activity in articular chondrocytes: its possible role in joint degeneration. Lab Invest 88:264–274
108. Yun MS, Kim SE, Jeon SH, Lee JS, Choi KY (2005) Both ERK and Wnt/beta-catenin pathways are involved in Wnt3a-induced proliferation. J Cell Sci 118:313–322
109. Zhen X, Wei L, Wu Q, Zhang Y, Chen Q (2001) Mitogen-activated protein kinase p38 mediates regulation of chondrocyte differentiation by parathyroid hormone. J Biol Chem 276:4879–4885
110. Zhu M, Chen M, Zuscik M, Wu Q, Wang YJ, Rosier RN, O'Keefe RJ, Chen D (2008) Inhibition of beta-catenin signaling in articular chondrocytes results in articular cartilage destruction. Arthritis Rheum 58:2053–2064