Functional integrin subunits regulating cell-matrix interactions in the intervertebral disc

被引:73
作者
Gilchrist, Christopher L.
Chen, Jun
Richardson, William J.
Loeser, Richard F.
Setton, Lori A.
机构
[1] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA
[2] Duke Univ, Med Ctr, Div Orthopaed Surg, Dept Surg, Durham, NC USA
[3] Wake Forest Univ, Sch Med, Sect Mol Med, Winston Salem, NC 27109 USA
关键词
integrin; intervertebral disc; collagen; fibronectin; laminin;
D O I
10.1002/jor.20343
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Cellular interactions with the extracellular matrix are key factors regulating cell survival, differentiation, and response to environmental stimuli in cartilagenous tissues. Much is known about the extracellular matrix proteins in the intervertebral disc (IVD) and their variations with region, age, or degenerative state of the tissue. In contrast, little is known of the integrin cell surface receptors that directly bind to and interact with these matrix proteins in the IVD. In almost all tissues, these integrin-mediated cell-matrix interactions are important for transducing environmental cues arising from mechanical stimuli, matrix degradation fragments, and cytokines into intracellular signals. In this study, cells from the nucleus pulposus and anulus fibrosus regions of porcine IVDs were analyzed via flow cytometry to quantify integrin expression levels upon isolation and after monolayer culture. Assays of cell attachment to collagens, fibronectin, and laminin were performed after functional blocking of select integrin subunits to evaluate the role of specific integrins in cell attachment. In situ distribution and co-localization of integrins and laminin were also characterized. Results identify integrin receptors critical for IVD cell interactions with collagens (alpha 1 beta 1) and fibronectin (alpha 5 beta 1). Additionally, dramatic differences in cell-laminin interactions were observed between cells of the nucleus and anulus regions, including differences in alpha 6 integrin expression, cell adhesion to laminin, and in situ pericellular environments. These findings suggest laminin-cell interactions may be important and unique to the nucleus pulposus region of the IVD. The results of this study provide new information on functional cell-matrix interactions in tissues of the IVD. (C) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
引用
收藏
页码:829 / 840
页数:12
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