Fibrin sealant promotes migration and proliferation of human articular chondrocytes: Possible involvement of thrombin and protease-activated receptors

  • Authors:
    • Yaowanuj Kirilak
    • Nathan J. Pavlos
    • Craig R. Willers
    • Renzhi Han
    • Haotian Feng
    • Jiake Xu
    • Nithiananthan Asokananthan
    • Geoffrey A. Stewart
    • Peter Henry
    • David Wood
    • Ming H. Zheng
  • View Affiliations

  • Published online on: April 1, 2006     https://doi.org/10.3892/ijmm.17.4.551
  • Pages: 551-558
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Abstract

Fibrin sealant (FS), a biological adhesive material, has been recently recommended as an adjunct in autologous chondrocyte implantation (ACI). While FS has been shown to possess osteoinductive potential, little is known about its effects on chondrogenic cells. In this study, we assessed the bioactivity of FS (Tisseel®) on the migration and proliferation of human articular chondrocytes in vitro. Using a co-culture assay to mimic matrix-induced ACI (MACI), chondrocytes were found to migrate from collagen membranes towards FS within 12 h of culture, with significant migratory activity evident by 24 h. In addition, 5-bromo-2'-deoxyuridine (BrdU) incorporation experiments revealed that thrombin, the active component of the tissue glue, stimulated chondrocyte proliferation, with maximal efficacy observed at 48 h post-stimulation (1-10 U/ml). In an effort to elucidate the molecular mechanisms underlying these thrombin-induced effects, we examined the expression and activation of protease-activated receptors (PARs), established thrombin receptors. Using a combination of RT-PCR and immunohistochemistry, all four PARs were detected in human chondrocytes, with PAR-1 being the major isoform expressed. Moreover, thrombin and a PAR-1, but not other PAR-isotype-specific peptide agonists, were found to induce rapid intracellular Ca2+ responses in human chondrocytes in calcium mobilization assays. Together, these data demonstrate that FS supports both the migration and proliferation of human chondrocytes. We propose that these effects are mediated, at least in part, via thrombin-induced PAR-1 signalling in human chondrocytes.

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April 2006
Volume 17 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kirilak Y, Pavlos NJ, Willers CR, Han R, Feng H, Xu J, Asokananthan N, Stewart GA, Henry P, Wood D, Wood D, et al: Fibrin sealant promotes migration and proliferation of human articular chondrocytes: Possible involvement of thrombin and protease-activated receptors. Int J Mol Med 17: 551-558, 2006
APA
Kirilak, Y., Pavlos, N.J., Willers, C.R., Han, R., Feng, H., Xu, J. ... Zheng, M.H. (2006). Fibrin sealant promotes migration and proliferation of human articular chondrocytes: Possible involvement of thrombin and protease-activated receptors. International Journal of Molecular Medicine, 17, 551-558. https://doi.org/10.3892/ijmm.17.4.551
MLA
Kirilak, Y., Pavlos, N. J., Willers, C. R., Han, R., Feng, H., Xu, J., Asokananthan, N., Stewart, G. A., Henry, P., Wood, D., Zheng, M. H."Fibrin sealant promotes migration and proliferation of human articular chondrocytes: Possible involvement of thrombin and protease-activated receptors". International Journal of Molecular Medicine 17.4 (2006): 551-558.
Chicago
Kirilak, Y., Pavlos, N. J., Willers, C. R., Han, R., Feng, H., Xu, J., Asokananthan, N., Stewart, G. A., Henry, P., Wood, D., Zheng, M. H."Fibrin sealant promotes migration and proliferation of human articular chondrocytes: Possible involvement of thrombin and protease-activated receptors". International Journal of Molecular Medicine 17, no. 4 (2006): 551-558. https://doi.org/10.3892/ijmm.17.4.551