Biomechanical Modulation of Collagen Fragment-induced Anabolic and Catabolic Activities in Chondrocyte/agarose Constructs

Overview

Journal Arthritis Res Ther

Publisher Biomed Central

Specialty Rheumatology

Date 2010 May 14

PMID 20462435

Citations 14

Authors

Tina T Chowdhury

Ronny M Schulz

Sonpreet S Rai

Christian B Thuemmler

Nico Wuestneck

Augustinus Bader

Gene A Homandberg

Affiliations

Soon will be listed here.

Abstract

Introduction: The present study examined the effect of collagen fragments on anabolic and catabolic activities by chondrocyte/agarose constructs subjected to dynamic compression.

Methods: Constructs were cultured under free-swelling conditions or subjected to continuous and intermittent compression regimes, in the presence of the N-terminal (NT) and C-terminal (CT) telopeptides derived from collagen type II and/or 1400 W (inhibits inducible nitric oxide synthase (iNOS)). The anabolic and catabolic activities were compared to the amino-terminal fibronectin fragment (NH2-FN-f) and assessed as follows: nitric oxide (NO) release and sulphated glycosaminoglycan (sGAG) content were quantified using biochemical assays. Tumour necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) release were measured by ELISA. Gene expression of matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), collagen type II and fibronectin were assessed by real-time quantitative polymerase chain reaction (qPCR). Two-way ANOVA and the post hoc Bonferroni-corrected t-test was used to examine data.

Results: The presence of the NT or CT peptides caused a moderate to strong dose-dependent stimulation of NO, TNFalpha and IL-1beta production and inhibition of sGAG content. In some instances, high concentrations of telopeptides were just as potent in stimulating catabolic activities when compared to NH2-FN-f. Depending on the concentration and type of fragment, the increased levels of NO and cytokines were inhibited with 1400 W, resulting in the restoration of sGAG content. Depending on the duration and type of compression regime employed, stimulation with compression or incubation with 1400 W or a combination of both, inhibited telopeptide or NH2-FN-f induced NO release and cytokine production and enhanced sGAG content. All fragments induced MMP-3 and MMP-13 expression in a time-dependent manner. This effect was reversed with compression and/or 1400 W resulting in the restoration of sGAG content and induction of collagen type II and fibronectin expression.

Conclusions: Collagen fragments containing the N- and C-terminal telopeptides have dose-dependent catabolic activities similar to fibronectin fragments and increase the production of NO, cytokines and MMPs. Catabolic activities were downregulated by dynamic compression or by the presence of the iNOS inhibitor, linking reparative activities by both types of stimuli. Future investigations which examine the signalling cascades of chondrocytes in response to matrix fragments with mechanical influences may provide useful information for early osteoarthritis treatments.

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References

Blain E, Mason D, Duance V . The effect of cyclical compressive loading on gene expression in articular cartilage. Biorheology. 2002; 40(1-3):111-7. View

Billinghurst R, Dahlberg L, Ionescu M, Reiner A, Bourne R, Rorabeck C . Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. J Clin Invest. 1997; 99(7):1534-45. PMC: 507973. DOI: 10.1172/JCI119316. View

Klatt A, Paul-Klausch B, Klinger G, Kuhn G, Renno J, Banerjee M . A critical role for collagen II in cartilage matrix degradation: collagen II induces pro-inflammatory cytokines and MMPs in primary human chondrocytes. J Orthop Res. 2008; 27(1):65-70. DOI: 10.1002/jor.20716. View

Lee D, Knight M . Mechanical loading of chondrocytes embedded in 3D constructs: in vitro methods for assessment of morphological and metabolic response to compressive strain. Methods Mol Med. 2004; 100:307-24. DOI: 10.1385/1-59259-810-2:307. View

Jeffrey J, Thomson L, Aspden R . Matrix loss and synthesis following a single impact load on articular cartilage in vitro. Biochim Biophys Acta. 1997; 1334(2-3):223-32. DOI: 10.1016/s0304-4165(96)00097-9. View

Felice B, Chichester C, Barrach H . Type II collagen peptide release from rabbit articular cartilage. Ann N Y Acad Sci. 1999; 878:590-3. DOI: 10.1111/j.1749-6632.1999.tb07736.x. View

Henrotin Y, Bruckner P, Pujol J . The role of reactive oxygen species in homeostasis and degradation of cartilage. Osteoarthritis Cartilage. 2003; 11(10):747-55. DOI: 10.1016/s1063-4584(03)00150-x. View

Jung M, Christgau S, Lukoschek M, Henriksen D, Richter W . Increased urinary concentration of collagen type II C-telopeptide fragments in patients with osteoarthritis. Pathobiology. 2004; 71(2):70-6. DOI: 10.1159/000074419. View

Homandberg G, Meyers R, Xie D . Fibronectin fragments cause chondrolysis of bovine articular cartilage slices in culture. J Biol Chem. 1992; 267(6):3597-604. View

10.

Pichika R, Homandberg G . Fibronectin fragments elevate nitric oxide (NO) and inducible NO synthetase (iNOS) levels in bovine cartilage and iNOS inhibitors block fibronectin fragment mediated damage and promote repair. Inflamm Res. 2004; 53(8):405-12. DOI: 10.1007/s00011-004-1279-8. View

11.

Lee D, Bader D . Compressive strains at physiological frequencies influence the metabolism of chondrocytes seeded in agarose. J Orthop Res. 1997; 15(2):181-8. DOI: 10.1002/jor.1100150205. View

12.

Jones K, Brown M, Ali S, BROWN R . An immunohistochemical study of fibronectin in human osteoarthritic and disease free articular cartilage. Ann Rheum Dis. 1987; 46(11):809-15. PMC: 1003397. DOI: 10.1136/ard.46.11.809. View

13.

Felson D, Kim Y . The futility of current approaches to chondroprotection. Arthritis Rheum. 2007; 56(5):1378-83. DOI: 10.1002/art.22526. View

14.

Kisiday J, Lee J, Siparsky P, Frisbie D, Flannery C, Sandy J . Catabolic responses of chondrocyte-seeded peptide hydrogel to dynamic compression. Ann Biomed Eng. 2009; 37(7):1368-75. DOI: 10.1007/s10439-009-9699-9. View

15.

Yasuda T . Cartilage destruction by matrix degradation products. Mod Rheumatol. 2006; 16(4):197-205. PMC: 2780665. DOI: 10.1007/s10165-006-0490-6. View

16.

Gemba T, Valbracht J, Alsalameh S, Lotz M . Focal adhesion kinase and mitogen-activated protein kinases are involved in chondrocyte activation by the 29-kDa amino-terminal fibronectin fragment. J Biol Chem. 2001; 277(2):907-11. DOI: 10.1074/jbc.M109690200. View

17.

Pfaffl M, Horgan G, Dempfle L . Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002; 30(9):e36. PMC: 113859. DOI: 10.1093/nar/30.9.e36. View

18.

Bonassar L, Grodzinsky A, Srinivasan A, Davila S, Trippel S . Mechanical and physicochemical regulation of the action of insulin-like growth factor-I on articular cartilage. Arch Biochem Biophys. 2000; 379(1):57-63. DOI: 10.1006/abbi.2000.1820. View

19.

Wong M, Siegrist M, Cao X . Cyclic compression of articular cartilage explants is associated with progressive consolidation and altered expression pattern of extracellular matrix proteins. Matrix Biol. 1999; 18(4):391-9. DOI: 10.1016/s0945-053x(99)00029-3. View

20.

Pulai J, Chen H, Im H, Kumar S, Hanning C, Hegde P . NF-kappa B mediates the stimulation of cytokine and chemokine expression by human articular chondrocytes in response to fibronectin fragments. J Immunol. 2005; 174(9):5781-8. PMC: 2903737. DOI: 10.4049/jimmunol.174.9.5781. View