β1-Integrin–collagen interaction reduces chondrocyte apoptosis

Cao, Liu; Lee, Vivian; Adams, Mark E.; Kiani, Chris; Zhang, Yaou; Hu, Wendy W.; Yang, Burton B.

doi:10.1016/s0945-053x(99)00027-x

Cited by 105 publications

(90 citation statements)

References 29 publications

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“…First, anti-␤1 blocking antibodies increase death of sternal chondrocytes in an organoid culture system (Hirsch et al 1997). Second, collagenase treatment of suspended chondrocyte cultures increases apoptosis, whereas readdition of collagen type I to the collagenase-digested cultures prevents apoptosis (Cao et al 1999). Finally, the absence of collagen II expression in cartilage in vivo is also associated with an increase of apoptotic chondrocytes (Yang et al 1997).…”

Section: ␤1 Integrins Regulate Cytokinesis Of Chondrocytes and Their mentioning

confidence: 99%

β1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis

Aszódi¹,

Hunziker²,

Brakebusch³

et al. 2003

Genes Dev.

292

275

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␤1 integrins are highly expressed on chondrocytes, where they mediate adhesion to cartilage matrix proteins. To assess the functions of ␤1 integrin during skeletogenesis, we inactivated the ␤1 integrin gene in chondrocytes. We show here that these mutant mice develop a chondrodysplasia of various severity. ␤1-deficient chondrocytes had an abnormal shape and failed to arrange into columns in the growth plate. This is caused by a lack of motility, which is in turn caused by a loss of adhesion to collagen type II, reduced binding to and impaired spreading on fibronectin, and an abnormal F-actin organization. In addition, mutant chondrocytes show decreased proliferation caused by a defect in G1/S transition and cytokinesis. The G1/S defect is, at least partially, caused by overexpression of Fgfr3, nuclear translocation of Stat1/Stat5a, and up-regulation of the cell cycle inhibitors p16 and p21. Altogether these findings establish that ␤1-integrin-dependent motility and proliferation of chondrocytes are mandatory events for endochondral bone formation to occur.[Keywords: Integrin; fibronectin; endochondral ossification; growth plate; cytokinesis; FGF] Supplemental material is available at http://www.genesdev.org.

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Section: ␤1 Integrins Regulate Cytokinesis Of Chondrocytes and Their mentioning

confidence: 99%

β1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis

Aszódi¹,

Hunziker²,

Brakebusch³

et al. 2003

Genes Dev.

292

275

View full text Add to dashboard Cite

show abstract

“…The specific factors that promote chondrocyte apoptosis are not fully understood. However, it is likely matrix disruption plays a major role through the loss of integrin-mediated pro-survival signals [9,10,24]. Integrins are cell surface molecules that facilitate binding to other cells and to extracellular matrix (ECM) components.…”

Section: Chondrocyte Apoptosis Regulation Pathwaysmentioning

confidence: 99%

“…Binding to specific ECM components such as collagen mediates cell survival through downstream kinase-mediated signaling pathways. Loss of this pro-survival signal has been shown to induce apoptosis in cultured chondrocytes, while addition of the appropriate receptor ligand rescues the cells from apoptotic cell death [9,10,24].…”

Section: Chondrocyte Apoptosis Regulation Pathwaysmentioning

confidence: 99%

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Chondrocyte Apoptosis: Implications for Osteochondral Allograft Transplantation

Kim

Teng

Dang

2008

Clin Orthop Relat Res

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Osteochondral allograft transplantation is a useful technique to manage larger articular cartilage injuries. One factor that may compromise the effectiveness of this procedure is chondrocyte cell death that occurs during the storage, preparation, and implantation of the osteochondral grafts. Loss of viable chondrocytes may negatively affect osteochondral edge integration and longterm function. A better understanding of the mechanisms responsible for chondrocyte loss could lead to interventions designed to decrease cell death and improve results. Recent studies indicate that apoptosis, or programmed cell death, is responsible for much of the chondrocyte death associated with osteochondral allograft transplantation. Theoretically, some of these cells can be rescued by blocking important apoptotic mediators. We review the role of apoptosis in cartilage degeneration, focusing on apoptosis associated with osteochondral transplantation. We also review the pathways thought to be responsible for regulating chondrocyte apoptosis, as well as experiments testing inhibitors of the apoptotic pathway. These data suggest that key contributors to the apoptotic process can be manipulated to enhance chondrocyte survival. This knowledge may lead to better surgical outcomes for osteochondral transplantation.

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“…Expression of cartilage-specific collagen type II is usually rapidly down-regulated in monolayer culture. The synthesis of cartilage-specifi c collagen type II and cell-matrix receptors β1-integrins which mediate the essential chondrocyte matrix interaction are the precondition for chondrocyte survival (Hirsh et al 1997;Cao et al 1999;Yang et al 1999). IL-10 is involved in extracellular matrix remodelling in other connective tissue cell types (Reitamo et al 1994;Yamamoto et al 2001;Moroguchi et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Cartilage-Specific Matrix and Integrin Expression in Three-Dimensional Articular Chondrocyte Cultures Overexpressing Human Interleukin-10

Müller

John

Kohl

et al. 2008

Clinical medicine. Arthritis and musculoskeletal disorders

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Interleukin (IL)-10 overexpression inhibits joint infl ammation, however the effect of high local concentrations of IL-10 on chondrocyte homeostasis remains unclear. The aim of this study was to determine the effects of IL-10 overexpression on cartilage matrix production in three-dimensional (3D) chondrocyte cultures. Human articular chondrocytes were transduced with adenoviral vectors alone (adv/empty) or by vectors either overexpressing enhanced green fl uorescence protein (adv/EGFP) or human IL-10 (adv/hIL-10) before their transfer to a 3D culture system. Non-transduced chondrocytes were used as controls. The expression of IL-10 or EGFP was confi rmed using ELISA or fl ow cytometry. Chondrocytes synthesis of collagen types II and I, aggrecan, fi bronectin and β1-integrin was determined over a period of 14 days post transduction using fl ow cytometry or immunohistochemistry. adv/EGFP or adv/IL-10 transduced chondrocytes expressed EGFP or secreted IL-10 detectable over the 2 weeks culture period. No suppression of collagen type II, aggrecan or β1-integrin synthesis by IL-10 overexpression was found and the deposition of collagen type I and fi bronectin remained unaffected compared to the controls. IL-10 overexpression does not impair key features of chondrocytes differentiated phenotype (e.g. collagen type II and aggrecan expression) suggesting the potential use of IL-10 for gene therapeutic approaches in the joint.

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β1-Integrin–collagen interaction reduces chondrocyte apoptosis

Cited by 105 publications

References 29 publications

β1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis

β1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis

Chondrocyte Apoptosis: Implications for Osteochondral Allograft Transplantation

Cartilage-Specific Matrix and Integrin Expression in Three-Dimensional Articular Chondrocyte Cultures Overexpressing Human Interleukin-10

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