The role of the extracellular matrix in articular chondrocyte regulation

S. P. Scully, jinwoo lee, M. A. Ghert, W. Qi

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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 α 1 (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 β 1 -integrin mediated mechanism to modulate the chondrocyte response to transforming growth factor-beta 1.

Original languageEnglish
JournalClinical Orthopaedics and Related Research
Issue number391 SUPPL.
DOIs
Publication statusPublished - 2001 Jan 1

Fingerprint

Collagen Type II
Chondrocytes
Extracellular Matrix
Joints
Transforming Growth Factor beta
Proteoglycans
Integrins
DNA
RNA
Hot Temperature
Integrin beta Chains
Cytokines
Gene Expression
Aggrecans
Procollagen
Bovine Serum Albumin
Collagen
Antibodies

All Science Journal Classification (ASJC) codes

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

@article{f6be19ee51b04fd1851a2d8b7c7f0ab3,
title = "The role of the extracellular matrix in articular chondrocyte regulation",
abstract = "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 α 1 (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 β 1 -integrin mediated mechanism to modulate the chondrocyte response to transforming growth factor-beta 1.",
author = "Scully, {S. P.} and jinwoo lee and Ghert, {M. A.} and W. Qi",
year = "2001",
month = "1",
day = "1",
doi = "10.1097/00003086-200110001-00008",
language = "English",
journal = "Clinical Orthopaedics and Related Research",
issn = "0009-921X",
publisher = "Springer New York",
number = "391 SUPPL.",

}

The role of the extracellular matrix in articular chondrocyte regulation. / Scully, S. P.; lee, jinwoo; Ghert, M. A.; Qi, W.

In: Clinical Orthopaedics and Related Research, No. 391 SUPPL., 01.01.2001.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The role of the extracellular matrix in articular chondrocyte regulation

AU - Scully, S. P.

AU - lee, jinwoo

AU - Ghert, M. A.

AU - Qi, W.

PY - 2001/1/1

Y1 - 2001/1/1

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 α 1 (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 β 1 -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 α 1 (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 β 1 -integrin mediated mechanism to modulate the chondrocyte response to transforming growth factor-beta 1.

UR - http://www.scopus.com/inward/record.url?scp=0034786674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034786674&partnerID=8YFLogxK

U2 - 10.1097/00003086-200110001-00008

DO - 10.1097/00003086-200110001-00008

M3 - Article

JO - Clinical Orthopaedics and Related Research

JF - Clinical Orthopaedics and Related Research

SN - 0009-921X

IS - 391 SUPPL.

ER -