Integrin expression by primary and immortalized human chondrocytes: evidence of a differential role for α1β1 and α2β1 integrins in mediating chondrocyte adhesion to types II and VI collagen

Loeser, Richard F.; Sadiev, Sagypash; Tan, Lujian; Goldring, Mary B.

doi:10.1053/joca.1999.0277

Cited by 167 publications

(142 citation statements)

References 38 publications

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“…The basement membrane type IV collagen and the beaded filaments forming type VI collagen can also be recognized by ␣ 1 ␤ 1 and ␣ 2 ␤ 1 integrins. However, ␣ 1 ␤ 1 seems to be a better receptor for them than for the fibrillar collagens (16,30). The receptors for other collagen subtypes, such as the fibril-associated collagens with interrupted triple-helices or transmembrane collagens, are less well known.…”

Section: Discussionmentioning

confidence: 95%

The Cell Adhesion Domain of Type XVII Collagen Promotes Integrin-mediated Cell Spreading by a Novel Mechanism

Nykvist¹,

Tasanen²,

Viitasalo³

et al. 2001

Journal of Biological Chemistry

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Type XVII collagen (BP180) is a keratinocyte transmembrane protein that exists as the full-length protein in hemidesmosomes and as a 120-kDa shed ectodomain in the extracellular matrix. The largest collagenous domain of type XVII collagen, COL15, has been described previously as a cell adhesion domain (Tasanen, K., Eble, J. A., Aumailley, M., Schumann, H., Baetge, J, Tu, H., Bruckner, P., and Bruckner-Tuderman, L. (2000) J. Biol. Chem. 275, 3093-3099). In the present work, the integrin binding of triple helical, human recombinant COL15 was tested. Solid phase binding assays using recombinant integrin ␣ 1 I, ␣ 2 I, and ␣ 10 I domains and cell spreading assays with ␣ 1 ␤ 1 -and ␣ 2 ␤ 1 -expressing Chinese hamster ovary cells showed that, unlike other collagens, COL15 was not recognized by the collagen receptors. Denaturation of the COL15 domain increased the spreading of human HaCaT keratinocytes, which could migrate on the denatured COL15 domain as effectively as on fibronectin. Spreading of HaCaT cells on the COL15 domain was mediated by ␣ 5 ␤ 1 and ␣ V ␤ 1 integrins, and it could be blocked by RGD peptides. The collagen ␣-chains in the COL15 domain do not contain RGD motifs but, instead, contain 12 closely related KGD motifs, four in each of the three ␣-chains. Twenty-two overlapping, synthetic peptides corresponding to the entire COL15 domain were tested; three peptides, all containing the KGD motif, inhibited the spreading of HaCaT cells on denatured COL15 domain. Furthermore, this effect was lost by mutation from D to E (KGE instead of KGD). We suggest that the COL15 domain of type XVII collagen represents a specific collagenous structure, unable to interact with the cellular receptors for other collagens. After being shed from the cell surface, it may support keratinocyte spreading and migration.The collagens are a family of extracellular matrix proteins (1). Among the 19 different collagen subtypes that have been identified, types XIII and XVII are the only transmembrane proteins (2, 3). Type XVII collagen (BP180) is hemidesmosomal transmembrane protein that is mutated in junctional epidermolysis bullosa and is targeted by autoantibodies in blistering skin diseases (4 -6). It occurs in two forms: as a full-length transmembrane protein and as a distinct, soluble ectodomain that is shed from the cell surface by a furin-mediated, proteolytic process (7,8). This collagen possesses intracellular and transmembrane domains that are of 560 and 23 amino acids in length, respectively. In addition, it has an extracellular domain of 914 amino acids that contains multiple noncollagenous interruptions, dividing it into 15 collagenous subdomains (3). The longest of these subdomains, COL15, consists of 242 amino acids (residues 567-808 of collagen XVII). Thus, it is much larger than any of the other collagenous domains, which vary from 14 to 45 residues in length (3).Most collagen subtypes can be recognized by a group of integrin-type cell adhesion receptors. Although all collagenreceptor integrins share the common ␤ 1 in...

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Section: Discussionmentioning

confidence: 95%

The Cell Adhesion Domain of Type XVII Collagen Promotes Integrin-mediated Cell Spreading by a Novel Mechanism

Nykvist¹,

Tasanen²,

Viitasalo³

et al. 2001

Journal of Biological Chemistry

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“…This cell line retains some of the specific phenotype of chondrocytes in long-term culture and is thus a suitable model for reproducible studies of chondrocyte metabolism (24)(25)(26). In chondrocytes, IL-1␤ and tumor necrosis factor rapidly activated the various members of the MAPK family, including ERK, JNK, and p38 MAPK (27)(28)(29).…”

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confidence: 99%

Up‐regulation of microsomal prostaglandin E synthase 1 in osteoarthritic human cartilage: Critical roles of the ERK‐1/2 and p38 signaling pathways

Masuko

Bérenbaum

Humbert

et al. 2004

Arthritis & Rheumatism

118

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Objective. Microsomal prostaglandin E synthase 1 (mPGES-1) is the final enzyme of the cascade that produces prostaglandin E 2 (PGE 2 ), a key actor in arthritis. To study mPGES-1 synthesis in human cartilage and its regulation by interleukin-1␤ (IL-1␤), we used human cartilage and an immortalized human chondrocyte cell line. Furthermore, we investigated the signaling pathways involved in mPGES-1 expression.Methods. We used real-time quantitative reverse transcription-polymerase chain reaction, Northern blotting, and Western blotting to measure mPGES-1 messenger RNA (mRNA) and protein expression in human chondrocytes. PGE 2 production was measured by enzyme-linked immunosorbent assay.Results. Cartilage specimens from osteoarthritis (OA) patients contained far greater amounts of mPGES-1 and cyclooxygenase 2 (COX-2) mRNA than did normal cartilage. Incubation with IL-1␤ markedly increased mPGES-1 mRNA and protein in a dosedependent and time-dependent manner, in parallel with an increase in PGE 2 levels. Both PD98059, an ERK pathway inhibitor, and SB203580, a p38␣/␤ MAPK inhibitor, abolished the increases in mPGES-1 mRNA and protein in response to IL-1␤. The specific p38␣ MAPK inhibitor SC906 suppressed IL-1␤-induced COX-2 expression but not IL-1␤-induced mPGES-1 expression, suggesting preferential involvement of p38␤ MAPK in IL-1␤-induced mPGES-1 expression.Conclusion. This study is the first to show that mPGES-1 is stimulated in human chondrocytes by the proinflammatory cytokine IL-1␤ via activation of both ERK-1/2 and p38 MAPK in an isoform-specific manner. We postulate that mPGES-1 may be a novel target for OA therapy.Prostaglandin E 2 (PGE 2 ) plays an important role in cartilage metabolism. Its many effects on chondrocytes (for review, see ref. 1) include enhanced production of matrix metalloproteinase 3 (2), modulation of proteoglycan and collagen synthesis (2,3), and stimulation of chondrocyte apoptosis (4,5). The synovial fluid of patients with osteoarthritis (OA) and rheumatoid arthritis contains high concentrations of PGE 2 (4), and cartilage and chondrocytes from OA patients spontaneously release more PGE 2 than does normal cartilage (2,6,7). These results suggest that PGE 2 may be actively involved in cartilage breakdown in OA patients. PGE 2 is synthesized by the isoenzymes cyclooxygenase 1 (COX-1) and COX-2, both of which act on arachidonic acid to form the prostaglandin endoperoxide H 2 (PGH 2 ). The prostanoid synthase prostaglandin E synthase (PGES) produces PGE 2 from PGH 2 . Three

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“…The looser collagen spacing possibly contributed to the significant increases in shDcn cellular deformation at higher strains. This network is bound to the cell membrane through HA core protein-CD44 interactions (Knudson et al, 1996), NG2 receptors (membrane bound chondroitin sulphate PGs) or through direct binding to the α1β1 integrin (Loeser et al, 2000). From our confocal images, the altered ColVI assembly in shDcn knockdown cells appeared as punctate localisations completely surrounding the cells at these binding sites.…”

Section: Jd Twomey Et Al Colvi and Dcn In Chondrogenic Hmsc Biophysicsmentioning

confidence: 87%

“…ColVI's interactions with the cell membrane at varying locations make it a primary candidate as a mechanotransducer (Poole et al, 1992;Doane et al, 1998;Loeser et al, 2000). This complex network assembles and integrates with the surrounding extracellular matrix (ECM) through interactions with type II collagen, aggrecan, and hyaluronan with aid from PGs such as DCN, BGN, as well as type IX collagen Keene et al, 1988;Bidanset et al, 1992;Poole et al, 1992;Wiberg et al, 2003;Nareyeck et al, 2004;Connelly et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Roles of type VI collagen and decorin in human mesenchymal stem cell biophysics during chondrogenic differentiation

Twomey¹,

Thakore²,

Hartman³

et al. 2014

eCM

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Human mesenchymal stem cells (hMSCs) induced towards chondrogenesis develop a pericellular matrix (PCM), rich in type VI collagen (ColVI) and proteoglycans such as decorin (DCN). Individual PCM protein functions still need to be elucidated to fully understand the mechanobiological role of this matrix. In this study we identified ColVI and DCN as important contributors in the mechanical function of the PCM and as biochemical modulators during chondrogenesis through targeted knockdown using shRNA lentiviral vectors. Gene expression, western blotting, immunofluorescence and cell deformation analysis were examined at 7, 14 and 28 days post chondrogenic induction. ColVI and DCN knockdown each affected gene expression of acan, bgn, and sox9 during chondrogenesis. ColVI was found to be of central importance in resisting applied strains, while DCN knockdown had strain dependent effects on deformation. We demonstrate that by using genetic engineering to control the biophysical microenvironment created by differentiating cells, it may be possible to guide cellular mechanotransduction.

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Integrin expression by primary and immortalized human chondrocytes: evidence of a differential role for α1β1 and α2β1 integrins in mediating chondrocyte adhesion to types II and VI collagen

Abstract: Immortalization with SV40-TAg results in altered integrin expression by chondrocytes. Changes in the relative levels of alpha1, alpha2, and alpha3 subunits may significantly alter the manner in which chondrocytes interact with types II and VI collagen in the extracellular matrix.

Cited by 167 publications

References 38 publications

The Cell Adhesion Domain of Type XVII Collagen Promotes Integrin-mediated Cell Spreading by a Novel Mechanism

The Cell Adhesion Domain of Type XVII Collagen Promotes Integrin-mediated Cell Spreading by a Novel Mechanism

Up‐regulation of microsomal prostaglandin E synthase 1 in osteoarthritic human cartilage: Critical roles of the ERK‐1/2 and p38 signaling pathways

Roles of type VI collagen and decorin in human mesenchymal stem cell biophysics during chondrogenic differentiation

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