[Phenotyping of chondrocytes from human osteoarthritic cartilage: chondrocyte expression of beta integrins and correlation with anatomic injury]

Chondrocyte-ECM (extracellular matrix) interactions are believed to play a pivotal role in the development and metabolic homeostasis of articular cartilage. Cell surface adhesion molecules have been reported to modulate chondrocyte binding to ECM (collagen, fibronectin, laminin) and they also act as transducers of critical signals in many biological processes such as growth, differentiation, migration and matrix synthesis. Recently, it has been shown that normal human articular chondrocytes strongly express beta1 integrins, which are constituted by a common chain (beta1) and a variable alphachain, but the behaviour of these molecules in human osteoarthritic cartilage has not been extensively investigated. We studied the expression of beta integrins (beta1-5, alpha1-6, av chains), LFA-1, ICAM-1 and CD44, on freshly isolated chondrocytes obtained from 10 osteoarthritic patients undergoing surgical knee replacement. Chondrocytes were isolated by enzymatic digestion from three zones of each articular cartilage with a differing degree of macroscopic and microscopic damage. Integrin expression and cell cycle analysis were carried out by flowcytometry. Chondrocytes from costal cartilages of 5 human foetuses were also studied. Chondrocytes from osteoarthritic cartilage expressed high levels of beta1 integrin and, at different percentages, all the alphachains. The alphachain most frequently expressed was alpha1, foilowed by alpha3, alpha5, alpha2, alphav. Integrin expression decreased from the least to the most damaged zone of articular cartilage and cell cycle analysis showed that proliferating chondrocytes (S phase) were prevalent on the latter zone. beta2, beta3, beta2, beta5, CD44, LFA-1/ICAM-1 complex were very low expressed. Fetal chondrocytes strongly expressed beta1 and beta5 chains. These data provide evidence to show that integrin expression on human chondrocytes changes in osteoarthritis and suggest that perturbations of chondrocyte-ECM signalling occur in the development of the disease. The different pattern of expression of beta1 and beta5 chains on adult and fetal chondrocytes leads to speculate that integrins play a key role in control of cartilage morphogenesis and differentiation.

[1]  K. Ostergaard,et al.  Expression of α and β subunits of the integrin superfamily in articular cartilage from macroscopically normal and osteoarthritic human femoral heads , 1998 .

[2]  W. Hornebeck,et al.  Increased expression of the Ed-B-containing fibronectin (an embryonic isoform of fibronectin) in human osteoarthritic cartilage. , 1996, British journal of rheumatology.

[3]  C. Rubin,et al.  Chondrocytes isolated from mature articular cartilage retain the capacity to form functional gap junctions , 1995, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[4]  T. Laurent,et al.  Functions of hyaluronan. , 1995, Annals of the rheumatic diseases.

[5]  R. Loeser,et al.  Expression of beta 1 integrins by cultured articular chondrocytes and in osteoarthritic cartilage. , 1995, Experimental cell research.

[6]  V. Pipitone,et al.  Expression of membrane-bound peptidases (CD10 and CD26) on human articular chondrocytes. Possible role of neuropeptidases in the pathogenesis of osteoarthritis. , 1995, Clinical and experimental rheumatology.

[7]  T. Hunter,et al.  Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase , 1994, Nature.

[8]  P. McCourt,et al.  Intercellular adhesion molecule-1 is a cell surface receptor for hyaluronan. , 1994, The Journal of biological chemistry.

[9]  Virgil L. Woods,et al.  Integrin expression by human articular chondrocytes. , 1994, Arthritis and rheumatism.

[10]  H. Kleinman,et al.  Integrin alpha 6 beta 4 mediates dynamic interactions with laminin. , 1994, Journal of cell science.

[11]  W. Knudson,et al.  Internalization of hyaluronan by chondrocytes occurs via receptor-mediated endocytosis. , 1993, Journal of cell science.

[12]  S. Goodman,et al.  Localization of beta 1-integrins in human cartilage and their role in chondrocyte adhesion to collagen and fibronectin. , 1993, Experimental cell research.

[13]  P. McKeown-Longo,et al.  The alpha v beta 5 integrin receptor regulates receptor-mediated endocytosis of vitronectin. , 1993, The Journal of biological chemistry.

[14]  D. Boettiger,et al.  Beta 1 integrins mediate chondrocyte interaction with type I collagen, type II collagen, and fibronectin. , 1993, Experimental cell research.

[15]  C B Knudson,et al.  Hyaluronan receptor-directed assembly of chondrocyte pericellular matrix , 1993, The Journal of cell biology.

[16]  L. Zardi,et al.  The inclusion of the type III repeat ED-B in the fibronectin molecule generates conformational modifications that unmask a cryptic sequence. , 1992, The Journal of biological chemistry.

[17]  Z. Werb,et al.  Signal transduction by integrin receptors for extracellular matrix: Cooperative processing of extracellular information , 1992, Current Biology.

[18]  G. Kingsley,et al.  Cellular responses to human chondrocytes: absence of allogeneic responses in the presence of HLA‐DR and ICAM‐1 , 1992, Clinical and experimental immunology.

[19]  Xiaoping Du,et al.  Inside-out integrin signalling , 1992, Current Biology.

[20]  R. Assoian,et al.  Cell attachment controls fibronectin and alpha 5 beta 1 integrin levels in fibroblasts. Implications for anchorage-dependent and -independent growth. , 1992, The Journal of biological chemistry.

[21]  D. Salter,et al.  Integrin expression by human articular chondrocytes. , 1992, British journal of rheumatology.

[22]  S. Nesbitt,et al.  Rat osteoclasts adhere to a wide range of rgd (arg‐gly‐asp) peptide‐containing proteins, including the bone sialoproteins and fibronectin, via a β3 integrin , 1992 .

[23]  S. Colucci,et al.  Recognition of osteopontin and related peptides by an alpha v beta 3 integrin stimulates immediate cell signals in osteoclasts. , 1991, The Journal of biological chemistry.

[24]  D. Ingber,et al.  Integrins as mechanochemical transducers. , 1991, Current opinion in cell biology.

[25]  B. Toole.  Hyaluronan and its binding proteins, the hyaladherins. , 1990, Current opinion in cell biology.

[26]  D Hamerman,et al.  The biology of osteoarthritis. , 1989, The New England journal of medicine.

[27]  Timothy A. Springer,et al.  Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1) , 1987, Cell.

[28]  H. Dorfman,et al.  Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. , 1971, The Journal of bone and joint surgery. American volume.

[29]  K. Sekiguchi,et al.  Distinct Structural Requirements for Interaction of the Integrins α5β1, αvβ5, and αvβ6 with the Central Cell Binding Domain in Fibronectin , 1996 .

[30]  J. Labat-Robert,et al.  Biosynthesis and distribution of fibronectin in normal and osteoarthritic human cartilage. , 1992, Clinical physiology and biochemistry.

[31]  J. Dingle,et al.  Expression of intercellular adhesion molecule 1 (ICAM-1) on human articular cartilage chondrocytes. , 1991, Connective tissue research.