Localization of β1-Integrins in Human Cartilage and Their Role in Chondrocyte Adhesion to Collagen and Fibronectin

Dürr, J.; Goodman, Simon L.; Potocnik, Alexandre J.; Mark, Helga von der; Mark, K von der

doi:10.1006/excr.1993.1189

Cited by 166 publications

(145 citation statements)

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“…3 for α2β1-integrin. In conclusion, these results confirm and extend previous observations [24,[39][40][41] that monomolecular cartilage collagens were good binding substrates for all collagen-binding integrins expressed by chondrocytes.…”

Section: Binding Of Soluble Integrins To Collagens II Ix and Xisupporting

confidence: 91%

The binding capacity of α1β1-, α2β1- and α10β1-integrins depends on non-collagenous surface macromolecules rather than the collagens in cartilage fibrils

et al. 2017

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Interactions of cells with supramolecular aggregates of the extracellular Matrix (ECM) are mediated, in part, by cell surface receptors of the integrin family. These are important molecular components of cell surfacesuprastructures regulating cellular activities in general. A subfamily of β1-integrins with von Willebrand-factor A-like domains (I-domains) in their α-chains can bind to collagen molecules and, therefore, are considered as important cellular mechano-receptors. Here we show that chondrocytes strongly bind to cartilage collagens in the form of individual triple helical molecules but very weakly to fibrils formed by the same molecules.We also find that chondrocyte integrins α1β1-, α2 β1-and α10β1-integrins and their I-domains have the same characteristics. Nevertheless we find integrin binding to mechanically generated cartilage fibril fragments, which also comprise peripheral non-collagenous material. We conclude that cell adhesion results from binding of integrin-containing adhesion suprastructures to the non-collagenous fibril periphery but not to the collagenous fibril cores. The biological importance of the well-investigated recognition of collagen molecules by integrins is unknown. Possible scenarios may include fibrillogenesis, fibril degradation and/orphagocytosis, recruitment of cells to remodeling sites, or molecular signaling across cytoplasmic membranes. In these circumstances, collagen molecules may lack a fibrillar organization. However, other processes requiring robust biomechanical functions, such as fibril organization in tissues, cell division, adhesion, or migration, do not involve direct integrin-collagen interactions.

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Section: Binding Of Soluble Integrins To Collagens II Ix and Xisupporting

confidence: 91%

The binding capacity of α1β1-, α2β1- and α10β1-integrins depends on non-collagenous surface macromolecules rather than the collagens in cartilage fibrils

et al. 2017

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“…The differential effects of IGF-1 and TGFP on chondrocyte cell surface levels of the alp1 integrin and on chondrocyte adhesion to type VI collagen suggest that the 2 growth factors have different effects on assembly and repair of the cyte adhesion to type 11 collagen despite a reduction in alp1 levels. Both alp1 and a2Pl integrins have been shown to mediate adhesion of fibrosarcoma (HT 1080) cells to type V1 collagen (23) and fetal chondrocytes or chondrosarcoma cells to type I1 collagen (8,24,25 unlike fetal chondrocytes and chondrosarcoma cells, adult articular chondrocytes do not appear to express significant amounts of a2pl (6,9), and an anti-a2 integrin blocking antibody did not block adhesion to type I1 collagen (10). A limitation of the present study is that it could not be directly determined whether IGF-1 or TGFP altered levels of a2pl since the a 2 subunit band comigrates with a3 and a5 and available antibodies do not recognize bovine a2.…”

Section: Discussionmentioning

confidence: 99%

“…Adult articular chondrocytes have been shown to express several different integrins, including a l p l , a3p1, a5p1, and avP5, with probably limited expression of avP3 (6)(7)(8)(9)(10). Members of the P1 subfamily of integrins serve as receptors for a number of ECM proteins, including certain collagens, laminin, and fibronectin.…”

Section: Growth Factors and Chondrocyte Integrins 271mentioning

confidence: 99%

Growth factor regulation of chondrocyte integrins. Differential effects of insulin‐like growth factor 1 and transforming growth factor β on α1β1 integrin expression and chondrocyte adhesion to type VI collagen

Loeser

1997

Arthritis & Rheumatism

119

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Objective. The ability of growth factors to modulate integrin expression may be important with regard to processes involved in tissue repair and remodeling. This study was undertaken to determine the effect of transforming growth factor β (TGFβ) and insulin‐like growth factor 1 (IGF‐1) on chondrocyte β1 integrin expression and integrin‐mediated adhesion to extracellular matrix proteins. Methods. Chondrocytes obtained from normal bovine articular cartilage were cultured in the presence or absence of 10% fetal bovine serum, 100 pM IGF‐1, or 100 pM TGF β. Integrin expression and function were measured by protein blotting of immunoprecipitated integrins, Northern blot analysis, and cell adhesion assays. Results. Immunoprecipitation with an anti–β1 integrin antibody coprecipitated the α1 integrin subunit and a band representing α3 and α5, as previously reported. Compared with serum‐free cultures, the use of serum resulted in an average 10‐fold increase in the α1 band and a 12‐fold increase in the α3/α5 band. IGF‐1 increased α1 and α3/α5 by an average of 3‐fold and 4‐fold, respectively. TGFβ also increased α3/α5 by >5‐fold but decreased α1 to an average of 24% of that found in serum‐free controls. Northern blot analysis revealed that TGFβ significantly increased α5 integrin subunit RNA levels. IGF‐1 did not have a significant effect on α5 or α1 integrin subunit RNA levels, suggesting that its effects on integrins are posttranscriptional. In cell adhesion assays, TGFβ treatment resulted in a 50% decrease in the adhesion of chondrocytes to type VI collagen, while adhesion to type II collagen and fibronectin was stimulated. IGF‐1 stimulated adhesion to all 3 proteins. An α1 integrin blocking antibody inhibited up to 75% of the adhesion of human chondrocytes to type VI collagen. Conclusion. Both IGF‐1 and TGFβ stimulate chondrocyte cell surface expression of the α3/α5 integrin subunit band and stimulate adhesion of chondrocytes to fibronectin and type II collagen. The 2 growth factors have opposite effects on expression of α1β1, with IGF‐1 increasing and TGFβ decreasing cell surface levels of this integrin. TGFβ‐treated cells also have decreased adhesion to type VI collagen. The opposing effects of IGF‐1 and TGFβ on chondrocyte expression of α1/β1 and on adhesion to type VI collagen suggest that α1β1 mediates chondrocyte adhesion to type VI collagen. This was confirmed by using an antibody to the α1 integrin subunit to block adhesion of chondrocytes to type VI collagen.

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“…integrins [18,19,35,45,46]. Integrins play a crucial role in early cartilage differentiation, since the presence of anti-integrin antibodies can inhibit differentiation of blastemal cells to chondroblasts [43].…”

Section: Introductionmentioning

confidence: 99%

Curcumin synergizes with resveratrol to stimulate the MAPK signaling pathway in human articular chondrocytes in vitro

2010

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The mitogen-activated protein kinase (MAPK) pathway is stimulated in differentiated chondrocytes and is an important signaling cascade for chondrocyte differentiation and survival. Pro-inflammatory cytokines such as interleukin 1b (IL-1b) play important roles in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA). In this study, we investigated whether curcumin and resveratrol can synergistically inhibit the catabolic effects of IL-1b, specifically the inhibition of the MAPK and subsequent apoptosis in human articular chondrocytes. Chondrocytes were either left untreated or treated with 10 ng/ml IL-1b or 1 lM U0126, a specific inhibitor of MAPK pathway alone for the indicated time periods or pretreated with 10 lM curcumin, 10 lM resveratrol or 10 lM resveratrol and 10 lM curcumin for 4 h followed by cotreatment with 10 ng/ml IL-1b or 1 lM U0126 and 10 lM resveratrol, 10 lM curcumin or 10 lM resveratrol and 10 lM curcumin for the indicated time periods. Cultures were evaluated by immunoblotting and transmission electron microscopy. Incubation of chondrocytes with IL-1b resulted in induction of apoptosis, downregulation of b1-integrins and the extracellular signal-regulated kinase 1/2 (Erk1/2). Interestingly, U0126 induced apoptosis and blocked the above-mentioned proteins in a similar way to IL-1b. Furthermore, curcumin and resveratrol inhibited IL-1b-or U0126-induced apoptosis and downregulation of b1-integrins and Erk1/2 in human articular chondrocytes. These results suggest that combining these two natural compounds activates MEK/Erk signaling, a pathway that is involved in the maintenance of chondrocyte differentiation and survival.

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Localization of β1-Integrins in Human Cartilage and Their Role in Chondrocyte Adhesion to Collagen and Fibronectin

Cited by 166 publications

References 0 publications

The binding capacity of α1β1-, α2β1- and α10β1-integrins depends on non-collagenous surface macromolecules rather than the collagens in cartilage fibrils

The binding capacity of α1β1-, α2β1- and α10β1-integrins depends on non-collagenous surface macromolecules rather than the collagens in cartilage fibrils

Growth factor regulation of chondrocyte integrins. Differential effects of insulin‐like growth factor 1 and transforming growth factor β on α1β1 integrin expression and chondrocyte adhesion to type VI collagen

Curcumin synergizes with resveratrol to stimulate the MAPK signaling pathway in human articular chondrocytes in vitro

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