The involvement of beta1 integrin in the modulation by collagen of chondrocyte-response to transforming growth factor-beta1.
The physiologic response of chondrocytes to maintenance of the matrix and response to injury likely involves signaling from multiple sources including soluble cytokines, mechanical stimulation, and signaling from the extracellular matrix. The signaling from the extracellular matrix may serve to effect cell differentiation and to modulate the response to cytokines. We have previously reported that type II collagen modulates the response of bovine articular chondrocytes to TGF-beta1. The molecular nature of the signaling mechanism has not been elucidated but presumably involves a similar mechanism by which the cell attaches to the surrounding matrix. An alginate bead culture system is utilized to which exogenous type II collagen is added. The inclusion of type II collagen results in an alteration of integrin expression with a down regulation of alpha2. The response of the chondrocyte to TGF-beta1 can be modulated by the inclusion of exogenous type II collagen. The modulation of DNA and proteoglycan synthesis was blocked by the treatment of anti-beta1 integrin antibody (4B4) or by cyclic RGD containing peptides. These events occur at concentrations that block cell adhesion to type II collagen. Linear RGD containing peptides and anti-anchorin antibodies had no effect on the modulation by type II collagen. These results suggest that type II collagen binding by chondrocytes at least in part occurs through the beta1 integrin. This binding results in modulation of the cell response to TGF-beta1. This modulation may serve to provide physiologic specificity to the cytokine-signaling cascade. An understanding of the regulatory milieu of the chondrocyte may permit the stimulation of an intrinsic repair of articular cartilage in the future. A near term application of this understanding can be made to tissue engineering attempts at articular cartilage repair.
Lee
Jin Woo
JW
Orthopedic Cell Biology Laboratory, Duke University Medical Center, Durham, North Carolina, USA.
Qi
Wen Ning
WN
Scully
Sean P
SP
D000464:Alginates; D000818:Animals; D017304:Annexin A5 / Q000276:immunology / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D002358:Cartilage, Articular / Q000166:cytology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D005110:Extracellular Space / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D019012:Integrin beta1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008863:Microspheres; D009842:Oligopeptides / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D000464:Alginates; D017304:Annexin A5; D000906:Antibodies; D024043:Collagen Type II; D006603:Hexuronic Acids; D019012:Integrin beta1; D009842:Oligopeptides; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C047981:arginyl-glycyl-aspartic acid; D020723:Glucuronic Acid; D004247:DNA