TY - JOUR
T1 - The role of the extracellular matrix in articular chondrocyte regulation
AU - Scully, S. P.
AU - Lee, J. W.
AU - Ghert, M. A.
AU - Qi, W.
PY - 2001
Y1 - 2001
N2 - The in vivo role of the extracellular matrix and the manner in which it interfaces with soluble regulators remains largely unknown. The current study reports the extracellular Type II collagen modulation of transforming growth factor beta 1-stimulated proliferation, proteoglycan synthesis, messenger ribonucleic acid expression for transforming growth factor-beta 1, and integrin messenger ribonucleic acid expression in articular chondrocytes from adults. This study shows that this cytokine modulation occurs through a mechanism initiated by the attachment of Type II collagen to the β1-integrin. Transforming growth factor-beta 1 stimulated deoxyribonucleic acid and proteoglycan synthesis in a bimodal fashion. Extracellular Type II collagen increased transforming growth factor-beta 1-stimulated deoxyribonucleic acid and proteoglycan synthesis, aggrecan gene expression as much as 400%, and α1(II) procollagen gene expression as much as 180% in a dose-dependent fashion. Heat inactivation of the Type II collagen abrogated the observed effects on deoxyribonucleic acid and proteoglycan synthesis. In contrast to Type II collagen, heat-denatured collagen and bovine serum albumin showed none of the observed effects. The presence of Type II collagen in the alginate bead cultures was found to diminish the messenger ribonucleic acid expression for α2 integrin and alter the cellular distribution pattern of the β1 integrin receptors. Blocking of the β1-integrin with cyclic-peptides containing the Arg-Gly-Asp sequences and antibodies reduced chondrocyte attachment to Type II collagen by 93%. The physiologic effects shown by the chondrocyte as a result of blocking this attachment to Type II collagen were a significant reduction in transforming growth factor-beta 1-stimulated deoxyribonucleic acid and proteoglycan synthesis. The conclusions elucidate the role played by the extracellular matrix in cytokine-specific regulation of the articular chondrocyte. The authors have shown that extracellular Type II collagen acts through a β1-integrin mediated mechanism to modulate the chondrocyte response to transforming growth factor-beta 1.
AB - The in vivo role of the extracellular matrix and the manner in which it interfaces with soluble regulators remains largely unknown. The current study reports the extracellular Type II collagen modulation of transforming growth factor beta 1-stimulated proliferation, proteoglycan synthesis, messenger ribonucleic acid expression for transforming growth factor-beta 1, and integrin messenger ribonucleic acid expression in articular chondrocytes from adults. This study shows that this cytokine modulation occurs through a mechanism initiated by the attachment of Type II collagen to the β1-integrin. Transforming growth factor-beta 1 stimulated deoxyribonucleic acid and proteoglycan synthesis in a bimodal fashion. Extracellular Type II collagen increased transforming growth factor-beta 1-stimulated deoxyribonucleic acid and proteoglycan synthesis, aggrecan gene expression as much as 400%, and α1(II) procollagen gene expression as much as 180% in a dose-dependent fashion. Heat inactivation of the Type II collagen abrogated the observed effects on deoxyribonucleic acid and proteoglycan synthesis. In contrast to Type II collagen, heat-denatured collagen and bovine serum albumin showed none of the observed effects. The presence of Type II collagen in the alginate bead cultures was found to diminish the messenger ribonucleic acid expression for α2 integrin and alter the cellular distribution pattern of the β1 integrin receptors. Blocking of the β1-integrin with cyclic-peptides containing the Arg-Gly-Asp sequences and antibodies reduced chondrocyte attachment to Type II collagen by 93%. The physiologic effects shown by the chondrocyte as a result of blocking this attachment to Type II collagen were a significant reduction in transforming growth factor-beta 1-stimulated deoxyribonucleic acid and proteoglycan synthesis. The conclusions elucidate the role played by the extracellular matrix in cytokine-specific regulation of the articular chondrocyte. The authors have shown that extracellular Type II collagen acts through a β1-integrin mediated mechanism to modulate the chondrocyte response to transforming growth factor-beta 1.
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U2 - 10.1097/00003086-200110001-00008
DO - 10.1097/00003086-200110001-00008
M3 - Article
C2 - 11603727
AN - SCOPUS:0034786674
SN - 0009-921X
VL - 391
SP - S72-S89
JO - Clinical Orthopaedics and Related Research
JF - Clinical Orthopaedics and Related Research
IS - SUPPL.
ER -