This Article Full Text Full Text (PDF) Letters to the Editor: Submit a response Alert me when this article is cited Alert me when Letters to the Editor are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fukui, N. Articles by Sandell, L. J. Search for Related Content PubMed PubMed Citation Articles by Fukui, N. Articles by Sandell, L. J. Social Bookmarking                   What's this?

Stimulation of BMP-2 Expression by Pro-Inflammatory Cytokines IL-1 and TNF- in Normal and Osteoarthritic Chondrocytes

Abstract

Background: Destruction of cartilage in osteoarthritis is a direct effect of an imbalance between catabolic and anabolic activities in the tissue. While a great deal is known about catabolism, we sought to determine the biochemical basis of the anabolic activity.

Methods: Cartilage was isolated from normal and osteoarthritic patients and subjected to both cell and explant culture. mRNA expression levels of the growth and differentiation factors bone morphogenetic protein-2 (BMP-2), BMP-4, BMP-6, cartilage-derived morphogenetic protein-1 (CDMP-1), connective tissue growth factor (CTGF), and activin were determined. BMP-2 was localized in osteoarthritic cartilage by immunohistochemistry. To determine the mechanism of BMP-2 stimulation, chondrocytes were cultured with TGF-ß (transforming growth factor-ß), insulin-like growth factor-1 (IGF-1), interleukin-1ß (IL-1ß), and tumor necrosis factor- (TNF-). The BMP-2 response was monitored by quantitative real-time polymerase chain reaction to ascertain mRNA levels and by Western blot analysis, BMP-2 protein quantitation, and immunohistochemistry to determine protein levels.

Results: BMP-2 was found to be up-regulated in osteoarthritic chondrocytes and cartilage. In cell culture, IL-1ß and TNF- increased BMP-2 mRNA and protein levels by eightfold and fifteenfold, respectively, whereas IGF-1 and TGF-ß1 had no effect. In cartilage explant cultures, IL-1ß and TNF- increased BMP-2 levels both intracellularly and extracellularly. Functional relevance was suggested by co-localization of BMP-2 and newly synthesized type-II procollagen within the same cells.

Conclusions: BMP-2 acts as a stimulus of anabolic activities in normal and osteoarthritic chondrocytes. Furthermore, the pro-inflammatory cytokines IL-1ß and TNF-, known to be present in synovium and cartilage of patients with osteoarthritis, stimulate the production of active BMP-2.

Clinical Relevance: These results suggest that, in addition to their role in catabolism of cartilage in osteoarthritis, the pro-inflammatory cytokines IL-1ß and TNF- may stimulate anabolic events through production of BMP-2. BMP-2, in turn, increases the synthesis of chondrocyte extracellular molecules, aggrecan and type-II collagen. Consequently, local inflammatory events may contribute to the remodeling or repair of cartilage.

CiteULike

Connotea

Del.icio.us

Facebook

Technorati

Twitter

This article has been cited by other articles:

				W.H. Lim, J. Toothman, J.H. Miller, R.H. Tallents, S.M. Brouxhon, M.E. Olschowka, and S. Kyrkanides IL-1{beta} Inhibits TGF{beta} in the Temporomandibular Joint Journal of Dental Research, June 1, 2009; 88(6): 557 - 562. [Abstract] [Full Text] [PDF]

				M B Goldring, M Otero, K Tsuchimochi, K Ijiri, and Y Li Defining the roles of inflammatory and anabolic cytokines in cartilage metabolism Ann Rheum Dis, December 1, 2008; 67(Suppl_3): iii75 - iii82. [Abstract] [Full Text] [PDF]

				H. H. Kariyawasam, G. Xanthou, J. Barkans, M. Aizen, A. B. Kay, and D. S. Robinson Basal Expression of Bone Morphogenetic Protein Receptor Is Reduced in Mild Asthma Am. J. Respir. Crit. Care Med., May 15, 2008; 177(10): 1074 - 1081. [Abstract] [Full Text] [PDF]

				E N Blaney Davidson, E L Vitters, P M van der Kraan, and W B van den Berg Expression of transforming growth factor-{beta} (TGF{beta}) and the TGF{beta} signalling molecule SMAD-2P in spontaneous and instability-induced osteoarthritis: role in cartilage degradation, chondrogenesis and osteophyte formation Ann Rheum Dis, November 1, 2006; 65(11): 1414 - 1421. [Abstract] [Full Text] [PDF]

				N. Fukui, Y. Ikeda, T. Ohnuki, A. Hikita, S. Tanaka, S. Yamane, R. Suzuki, L. J. Sandell, and T. Ochi Pro-inflammatory Cytokine Tumor Necrosis Factor-{alpha} Induces Bone Morphogenetic Protein-2 in Chondrocytes via mRNA Stabilization and Transcriptional Up-regulation J. Biol. Chem., September 15, 2006; 281(37): 27229 - 27241. [Abstract] [Full Text] [PDF]

				H. Takahashi, N. Goto, Y. Kojima, Y. Tsuda, Y. Morio, M. Muramatsu, and Y. Fukuchi Downregulation of type II bone morphogenetic protein receptor in hypoxic pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L450 - L458. [Abstract] [Full Text] [PDF]

				G Tardif, J-P Pelletier, D Hum, C Boileau, N Duval, and J Martel-Pelletier Differential regulation of the bone morphogenic protein antagonist chordin in human normal and osteoarthritic chondrocytes Ann Rheum Dis, February 1, 2006; 65(2): 261 - 264. [Abstract] [Full Text] [PDF]

				K. A. Hruska, S. Mathew, and G. Saab Bone Morphogenetic Proteins in Vascular Calcification Circ. Res., July 22, 2005; 97(2): 105 - 114. [Abstract] [Full Text] [PDF]

Stanford University Libraries' HighWire Press (TM) assists in the publication of JBJS Online.
Copyright © 2003 by The Journal of Bone and Joint Surgery, Inc. Online ISSN: 1535-1386.
The Journal of Bone and Joint Surgery®, JBJS®, JB&JS®, and eJBJS® are registered in the U.S. Patent and Trademark Office.