Mechanical responses and integrin associated protein expression by human ankle chondrocytes

Issue title: Selected papers of the 4th International Symposium on Mechanobiology of Cartilage and Chondrocyte, Budapest, 20–22 May, 2006

Article type: Research Article

Authors: Orazizadeh, M. | Cartlidge, C. | Wright, M.O. | Millward-Sadler, S.J. | Nieman, J. | Halliday, B.P. | Lee, H.-S. | Salter, D.M.^;

Affiliations: Department of Histology, School of Medicine, Ahwaz University of Medical Sciences, Ahwaz, Iran | Division of Pathology, School of Molecular and Clinical Medicine, College of Medicine and Veterinary Medicine, Edinburgh University, UK | Department of Pathology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan

Note: [] Address for correspondence: D.M. Salter, Pathology, Edinburgh Royal Infirmary, Little France Crescent, Edinburgh, EH16 4AS, UK. Tel.: +44 131 242 7125; Fax: +44 131 242 7169; E-mail: donald.salter@ed.ac.uk.

Abstract: Metabolic, biochemical and biomechanical differences between ankle and knee joint cartilage and chondrocytes including resistance to the effects of catabolic cytokines and fibronectin fragments may be relevant to differences in prevalence of OA in these joints. Although there is increasing information available on how chondrocytes from knee and hip joint cartilage recognise and respond to mechanical stimuli, knowledge of mechanotransduction in ankle joint chondrocytes is limited. This study was undertaken to (i) establish whether the response of normal ankle joint derived chondrocytes to mechanical stimulation in vitro was similar to that of normal and osteoarthritic knee joint derived chondrocytes and (ii) to investigate whether these chondrocytes showed differences in expression of integrin associated regulatory and signalling molecules. Unlike normal knee joint chondrocytes, ankle joint chondrocytes did not show an increase in relative levels of aggrecan mRNA when mechanically stimulated. No obvious change in protein tyrosine phosphorylation was seen in ankle chondrocytes subsequent to mechanical stimulation but these cells expressed elevated levels of tyrosine phosphorylated proteins at rest when compared to normal knee joint chondrocytes. Ankle joint chondrocytes showed an increase in protein kinase B phosphorylation following 1 min 0.33 Hz stimulation which was inhibited by the presence of antibodies to α5β1 integrin. Ankle joint chondrocytes appeared to show significant differences in levels of the integrin-associated proteins CD98, CD147 and galectin 3, PKCγ and differences in responses to glutamate were seen. Chondrocytes from ankle and knee joint cartilage respond differently to 0.33 Hz mechanical stimulation. This may be related to modified integrin-dependent mechanotransduction as a result of changes in expression of integrin regulatory molecules such as CD98 or differential expression and function of downstream components of the mechanotransduction pathway such as PKC or NMDA receptors.

Keywords: Cartilage, PKB, integrin, aggrecan

Journal: Biorheology, vol. 43, no. 3-4, pp. 249-258, 2006