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http://dx.doi.org/10.5352/JLS.2011.21.4.534

Retinoic Acid Potentiates Nitric Oxide-Induced Dedifferentiation through the ERK Pathway in Rabbit Articular Chondrocytes  

Yu, Seon-Mi (Department of Biological Sciences, College of Natural Sciences, Kongju National University)
Kim, Song-Ja (Department of Biological Sciences, College of Natural Sciences, Kongju National University)
Publication Information
Journal of Life Science / v.21, no.4, 2011 , pp. 534-541 More about this Journal
Abstract
Retinoic acid (RA), a metabolite of vitamin A, is known to regulate dedifferentiation of rabbit articular chondrocytes. The regulatory mechanism of dedifferentiation by RA is not yet understood. Thus, the effect of RA on the regulation of nitric oxide (NO)-induced dedifferentiation was investigated in rabbit articular chondrocytes. RA caused loss of the differentiated chondrocyte phenotype as demonstrated by inhibition of type II collagen expression and proteoglycan synthesis. RA also accelerated NO-induced dedifferentiation in rabbit articular chondrocytes as detected by expression of type II collagen and Sox-9 using Western blot analysis and production of sulfated proteoglycan using Alcain blue staining. Further, RA potentiated NO-induced activation of ERK. Inhibition of ERK with PD98059 (PD) recovered the expression of type II collagen and Sox-9 and production of sulfate proteoglycan in NO-induced dedifferentiated chondrocytes by RA treatment. Our findings suggest that RA accelerates NO-induced dedifferentiation of rabbit articular chondrocytes via the ERK pathway.
Keywords
Chondrocytes; retinoic acid (RA); nitric oxide (NO); dedifferentiation;
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1 Kwasigroch, T. E. and D. M. Kochhar. 1980. Production of congenital limb defects with retinoic acid: phenomenological evidence of progressive differentiation during limb morphogenesis. Anat. Embryol. (Berl). 161, 105-113.   DOI
2 L'Hermette, M. F., C. Tourny-Chollet, G. Polle, and F. H. Dujardin. 2006. Articular cartilage, degenerative process, and repair: current progress. Int. J. Sports Med. 27, 738-744.   DOI
3 Cao, M., A. Westerhausen-Larson, C. Niyibizi, K. Kavalkovich, H. I. Georgescu, C. F. Rizzo, P. A. Hebda, M. Stefanovic-Racic, and C. H. Evans. 1997. Nitric oxide inhibits the synthesis of type-II collagen without altering Col2A1 mRNA abundance: prolyl hydroxylase as a possible target. Biochem. J. 324, 305-310.
4 Cash, D. E., C. B. Bock, K. Schughart, E. Linney, and T. M. Underhill. 1997. Retinoic acid receptor alpha function in vertebrate limb skeletogenesis: a modulator of chondrogenesis. J. Cell Biol. 136, 445-457.   DOI
5 Cho, S. H., C. D. Oh, S. J. Kim, I. C. Kim, and J. S. Chun. 2003. Retinoic acid inhibits chondrogenesis of mesenchymal cells by sustaining expression of N-cadherin and its associated proteins. J. Cell Biochem. 89, 837-847.   DOI
6 DeLise, A. M., L. Fischer, and R. S. Tuan. 2000. Cellular interactions and signaling in cartilage development. Osteoarthritis Cartilage 8, 309-334.   DOI
7 Demoor-Fossard, M., P. Galera, M. Santra, R. V. Iozzo, J. P. Pujol, and F. Redini. 2001. A composite element binding the vitamin D receptor and the retinoic X receptor alpha mediates the transforming growth factor-beta inhibition of decorin gene expression in articular chondrocytes. J. Biol. Chem. 276, 36983-36992.   DOI
8 Eyre, D. 2002. Collagen of articular cartilage. Arthritis Res. 4, 30-35.
9 Underhill, T. M. and A. D. Weston. 1998. Retinoids and their receptors in skeletal development. Microsc. Res. Tech. 43, 137-155.   DOI
10 Weston, A. D., V. Rosen, R. A. Chandraratna, and T. M. Underhill. 2000. Regulation of skeletal progenitor differentiation by the BMP and retinoid signaling pathways. J. Cell Biol. 148, 679-690.   DOI
11 Yoon, E. K., W. K. Lee, J. H. Lee, S. M. Yu, S. G. Hwang, and S. J. Kim. 2007. ERK-1/-2 and p38 kinase oppositely regulate 15-deoxy-delta(12,14)-prostaglandinJ(2)-Induced PPAR-gamma activation that mediates dedifferentiation but not cyclooxygenase-2 expression in articular chondrocytes. J. Korean Med. Sci. 22, 1015-1021.   DOI   ScienceOn
12 Yoon, J. B., S. J. Kim, S. G. Hwang, S. Chang, S. S. Kang, and J. S. Chun. 2003. Non-steroidal anti-inflammatory drugs inhibit nitric oxide-induced apoptosis and dedifferentiation of articular chondrocytes independent of cyclooxygenase activity. J. Biol. Chem. 278, 15319-15325.   DOI
13 Sandell, L. J. and P. Adler. 1999. Developmental patterns of cartilage. Front Biosci. 4, D731-742.   DOI
14 Martel-Pelletier, J., C. Boileau, J. P. Pelletier, and P. J. Roughley. 2008. Cartilage in normal and osteoarthritis conditions. Best Pract. Res. Clin. Rheumatol. 22, 351-384.   DOI   ScienceOn
15 Notoya, K., D. V. Jovanovic, P. Reboul, J. Martel-Pelletier, F. Mineau, and J. P. Pelletier. 2000. The induction of cell death in human osteoarthritis chondrocytes by nitric oxide is related to the production of prostaglandin E2 via the induction of cyclooxygenase-2. J. Immunol. 165, 3402-3410.   DOI
16 Poole, A. R. 1999. An introduction to the pathophysiology of osteoarthritis. Front Biosci. 4, D662-670.   DOI
17 Sandell, L. J. and T. Aigner. 2001. Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Res. 3, 107-113.   DOI
18 Solursh, M. and S. Meier. 1973. The selective inhibition of mucopolysaccharide synthesis by vitamin A treatment of cultured chick embryo chondrocytes. Calcif. Tissue Res. 13, 131-142.   DOI
19 Tamura, T., T. Nakanishi, Y. Kimura, T. Hattori, K. Sasaki, H. Norimatsu, K. Takahashi, and M. Takigawa. 1996. Nitric oxide mediates interleukin-1-induced matrix degradation and basic fibroblast growth factor release in cultured rabbit articular chondrocytes: a possible mechanism of pathological neovascularization in arthritis. Endocrinology 137, 3729-3737.   DOI
20 Taskiran, D., M. Stefanovic-Racic, H. Georgescu, and C. Evans. 1994. Nitric oxide mediates suppression of cartilage proteoglycan synthesis by interleukin-1. Biochem. Biophys. Res. Commun. 200, 142-148.   DOI
21 Abramson, S. B., M. Attur, A. R. Amin, and R. Clancy. 2001. Nitric oxide and inflammatory mediators in the perpetuation of osteoarthritis. Curr. Rheumatol. Rep. 3, 535-541.   DOI
22 Goldring, M. B., J. R. Birkhead, L. F. Suen, R. Yamin, S. Mizuno, J. Glowacki, J. L. Arbiser, and J. F. Apperley. 1994. Interleukin-1 beta-modulated gene expression in immortalized human chondrocytes. J. Clin. Invest. 94, 2307-2316.   DOI
23 Hassell, J. R., J. P. Pennypacker, and C. A. Lewis. 1978. Chondrogenesis and cell proliferation in limb bud cell cultures treated with cytosine arabinoside and vitamin A. Exp. Cell Res. 112, 409-417.   DOI
24 Jiang, H., D. R. Soprano, S. W. Li, K. J. Soprano, J. D. Penner, M. Gyda 3rd, and D. M. Kochhar. 1995. Modulation of limb bud chondrogenesis by retinoic acid and retinoic acid receptors. Int. J. Dev. Biol. 39, 617-627.
25 Kim, S. J., S. G. Hwang, D. Y. Shin, S. S. Kang, and J. S. Chun. 2002. p38 kinase regulates nitric oxide-induced apoptosis of articular chondrocytes by accumulating p53 via NFkappa B-dependent transcription and stabilization by serine 15 phosphorylation. J. Biol. Chem. 277, 33501-33508.   DOI
26 Tsonis, P. A., M. T. Sargent, K. Del Rio-Tsonis, and J. C. Jung. 1996. 9-cis retinoic acid antagonizes the stimulatory effect of 1,25 dihydroxyvitamin D3 on chondrogenesis of chick limb bud mesenchymal cells: interactions of their receptors. Int. J. Dev. Biol. 40, 1053-1059.
27 Kim, S. J. and J. S. Chun. 2003. Protein kinase C alpha and zeta regulate nitric oxide-induced NF-kappa B activation that mediates cyclooxygenase-2 expression and apoptosis but not dedifferentiation in articular chondrocytes. Biochem. Biophys. Res. Commun. 303, 206-211.   DOI   ScienceOn
28 Kim, S. J., S. G. Hwang, I. C. Kim, and J. S. Chun. 2003. Actin cytoskeletal architecture regulates nitric oxide-induced apoptosis, dedifferentiation, and cyclooxygenase-2 expression in articular chondrocytes via mitogen-activated protein kinase and protein kinase C pathways. J. Biol. Chem. 278, 42448-42456.   DOI
29 Kim, S. J., J. W. Ju, C. D. Oh, Y. M. Yoon, W. K. Song, J. H. Kim, Y. J. Yoo, O. S. Bang, S. S. Kang, and J. S. Chun. 2002. ERK-1/2 and p38 kinase oppositely regulate nitric oxide-induced apoptosis of chondrocytes in association with p53, caspase-3, and differentiation status. J. Biol. Chem. 277, 1332-1339.   DOI
30 Kim, S. J., H. G. Kim, C. D. Oh, S. G. Hwang, W. K. Song, Y. J. Yoo, S. S. Kang, and J. S. Chun. 2002. p38 kinase-dependent and-independent Inhibition of protein kinase C zeta and-alpha regulates nitric oxide-induced apoptosis and dedifferentiation of articular chondrocytes. J. Biol. Chem. 277, 30375-30381.   DOI
31 Biddulph, D. M., M. M. Dozier, N. C. Julian, and L. M. Sawyer. 1988. Inhibition of chondrogenesis by retinoic acid in limb mesenchymal cells in vitro: effects on PGE2 and cyclic AMP concentrations. Cell Differ. Dev. 25, 65-75.   DOI
32 Amin, A. R. and S. B. Abramson. 1998. The role of nitric oxide in articular cartilage breakdown in osteoarthritis. Curr. Opin. Rheumatol. 10, 263-268.   DOI
33 Amin, A. R., M. Attur, and S. B. Abramson. 1999. Nitric oxide synthase and cyclooxygenases: distribution, regulation, and intervention in arthritis. Curr. Opin. Rheumatol. 11, 202-209.   DOI