Extracellular matrix protein expression in terminally differentiating chondrocytes is integrin mediated.
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Hyaline cartilage is an avascular tissue involved in growth and development of the skeletal system. Prior to bone deposition, chondrocytes terminally differentiate into hypertrophic chondrocytes and produce type X collagen. Controlled regulation of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) contribute to cartilage avascularity. We asked, Do inlegrin receptors have a role in chondrocyte terminal differentiation and gene expression, and Do MMP and TIMP expression change with chondrocyte terminal differentiation? It has previously been shown that whole embryonic sterna grown in defined media are morphologically and phenotypically similar to developing in ovo sterna (IOS). To determine if cell-ECM interactions were necessary for chondrocyte terminal differentiation, collagen integrin receptor antibodies were added to culture media. Addition of an anti-1, -2 or -3 integrin antibody inhibited cell-ECM interactions, chondrocyte hypertrophy, type X collagen expression and sternal growth. Sterna cultured with integrin antibodies had fewer ECM connections and an altered actin distribution. Western blot analysis and zymography identified TIMPs and MMPs, respectively, in OCS conditioned media. Control sterna produced chondrocyte derived inhibitor (ChDI) and TIMP-1. Sterna cultured with integrin antibodies produced ChDI, TIMP-1, TIMP-2 and TIMP-3. Zymography with control OCS produced the 72 kDa-gelatinase, whereas the 72 and 92 kDa-gelatinases were produced by OCS grown with integrin antibodies. These results suggested that cell-ECM interactions via integrin receptors were necessary for processes that occur prior to angiogenesis and bone deposition, including: sternal growth, chondrocyte terminal differentiation and TIMP/MMP regulation.
