Apoptosis of Chondrocytes in Transgenic Mice Lacking Collagen II

Yang, Chunlin; Li, Shiwu; Helminen, Heikki J.; Khillan, Jaspal S.; Bao, Yunhua; Prockop, Darwin J.

doi:10.1006/excr.1997.3692

Cited by 102 publications

(70 citation statements)

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“…Chondrocyte loss certainly has profound effects on ECM composition; conversely, ECM composition has an equally profound effect on chondrocytes viability. Transgenic mice lacking type 11 collagen cannot support the survival of chondrocytes due to the induction of apoptosis [21]. Furthermore, collagen degradation induces apoptosis in chondrocytes grown in suspension culture, an effect that can be reversed by the addition of exogenous collagen [2].…”

Section: Discussionmentioning

confidence: 99%

Chondrocyte apoptosis induced by collagen degradation: Inhibition by caspase inhibitors and IGF‐1

Lo¹,

Kim²

2004

Journal Orthopaedic Research

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The main objective of this study was to test the effectiveness of candidate apoptosis inhibitors in limiting chondrocyte apoptosis induced by collagen degradation. Primary human chondrocytes were isolated from normal articular cartilage and grown in monolayer culture. Collagenase was added to the cells in the presence and absence of caspase inhibitors and insulin like growth factor (1GF)-I . The amount of chondrocyte apoptosis was measured using an enzyme linked immunosorbent assay for nucleosomes, a specific and quantitative measure of apoptosis. Chondrocyte apoptosis was induced by collagenase treatment in both a time and dose dependent manner. The non-selective caspase inhibitor Z-VAD, the caspase-3 selective inhibitor Z-DEVD, and the growth factor insulin like growth factor (1GF)-I inhibited chondrocyte apoptosis induced by collagenase treatment. The caspase-l selective inhibitor Z-YVAD also blocked chondrocyte apoptosis under these conditions, in contrast to previous studies where caspase-1 inhibition failed to block apoptosis induced by agents such as the topoisomerase inhibitor camptothecin. These data demonstrate that the response of chondrocytes to caspase inhibition may be dependent upon the specific stimulus that initiates apoptosis. Furthermore, these findings suggest that multiple pathways involving both the initiation and execution of programmed cell death are potential targets for chondrocyte apoptosis inhibition therapy.

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Section: Discussionmentioning

confidence: 99%

Chondrocyte apoptosis induced by collagen degradation: Inhibition by caspase inhibitors and IGF‐1

Lo¹,

Kim²

2004

Journal Orthopaedic Research

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“…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). Integrins can inhibit programmed cell death by activation of Erk, the FAK-Rac1-JNK pathway, or activation of Akt through FAK and PI3K (Giancotti and Rouslahti 1999).…”

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.

291

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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“…They activate different signal transduction pathways, such as the mitogen-activated protein (MAP) kinase pathway, and thus control proliferation, differentiation and survival of tenocytes [18,19]. Undisturbed cell-matrix interactions are essential for cell viability, and inhibition of the MAP kinase pathway can induce programmed cell death [20,21].…”

Section: Introductionmentioning

confidence: 99%

Synergistic effects of dexamethasone and quinolones on human-derived tendon cells

Sendzik

Shakibaei

Schäfer‐Korting

et al. 2010

International Journal of Antimicrobial Agents

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Quinolones and glucocorticoids are frequently used drugs that may cause tendinopathy as a rare adverse effect. We exposed human tenocyte cultures to the steroid dexamethasone alone or in combination with either ciprofloxacin or levofloxacin at concentrations of 3 mg/L and 10 mg/L. At concentrations corresponding to peak levels in plasma and tissues during therapy (ca. 3-10 mg/L), ciprofloxacin caused a significant decrease in collagen type I and the 1 -integrin receptor. In contrast, no corresponding effect was induced by 3 mg/L levofloxacin.With both quinolones at 3 mg/L and 10 mg/L, the amount of matrix metalloproteinase-1 (MMP-1) and MMP-13 was increased. In addition, 3 mg/L ciprofloxacin and 10 mg/L levofloxacin activated caspase-3. Apoptotic changes were confirmed by electron microscopy. Incubation of human tenocytes with dexamethasone decreased the main matrix protein collagen type I, the

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Apoptosis of Chondrocytes in Transgenic Mice Lacking Collagen II

Cited by 102 publications

References 0 publications

Chondrocyte apoptosis induced by collagen degradation: Inhibition by caspase inhibitors and IGF‐1

Chondrocyte apoptosis induced by collagen degradation: Inhibition by caspase inhibitors and IGF‐1

β1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis

Synergistic effects of dexamethasone and quinolones on human-derived tendon cells

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