Substrate architecture and fluid-induced shear stress during chondrocyte seeding: Role of α5β1 integrin

Spiteri, Caroline G.; Young, Elton T.; Simmons, Craig A.; Kandel, Rita A.; Pilliar, Robert M.

doi:10.1016/j.biomaterials.2008.01.018

Cited by 12 publications

(7 citation statements)

References 28 publications

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“…In ongoing studies we have observed changes in chondrocyte cell shape following mechanical loading (unpublished data). We have also found that chondrocyte spreading in this system involves integrins 46. It is possible that cell shape and integrin activation is mediating MT1‐MMP expression.…”

Section: Discussionsupporting

confidence: 56%

Improved bioengineered cartilage tissue formation following cyclic compression is dependent on upregulation of MT1‐MMP

Croos

Roughley

Kandel

2010

Journal Orthopaedic Research

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The generation of bioengineered cartilage tissue suitable for transplantation is a potential therapy to treat damaged cartilage. We have shown previously that the physical and biomechanical properties of bioengineered cartilage can be improved by the application of 30 min of cyclic compression by a mechanism involving sequential upregulation of gene and protein levels of membrane type-1 matrix metalloproteinase (MT1-MMP) and MMP-13. In the current study, we demonstrated that MT1-MMP is critical to this response, as blocking the upregulation of MT1-MMP prevented the improvement in tissue formation. MT1-MMP seems to act by inducing tissue remodeling as evidenced by the presence of aggrecan degradation products by Western blot analysis and increased release of matrix molecules into the media. Release of these molecules was diminished when MT1-MMP upregulation was prevented. This matrix degradation was likely due to MT1-MMP, as under conditions where MMP-13 expression is maintained (stimulation in the presence of MT1-MMP siRNA) the release of these matrix molecules into the media was still prevented. It also appears that MT1-MMP does not regulate MMP-13 gene expression, as MT1-MMP-siRNA pretreatment had no effect on MMP-13 expression following mechanical stimulation. Further analysis of the anabolic genes and proteins involved in mechanically stimulated cartilage will lead to better understanding of the mechanism(s) underlying tissue formation yielding improved bioengineered cartilage. ß

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Section: Discussionsupporting

confidence: 56%

Improved bioengineered cartilage tissue formation following cyclic compression is dependent on upregulation of MT1‐MMP

Croos

Roughley

Kandel

2010

Journal Orthopaedic Research

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“…In chondrocytes, mechanical stimuli have been shown to alter actin cytoskeletal organization16, 17 and chondrocyte morphology 10. We have also shown previously that fluid flow‐induced shear forces stimulate α5β1 integrin dependent cell spreading,18 which were associated with an increase in collagen and proteoglycan accumulation 19. Takino et al proposed that integrin clustering is induced by MT1‐MMP,20 which raises the possibility that cyclic compression may cause changes in cell shape that ultimately leads to alteration in cell matrix synthesis.…”

Section: Introductionmentioning

confidence: 61%

Matrix accumulation by articular chondrocytes during mechanical stimulation is influenced by integrin‐mediated cell spreading

Spiteri

Raizman

Pilliar

et al. 2010

J Biomedical Materials Res

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We have shown previously that cyclic compression of newly forming bioengineered cartilage in vitro results in improved tissue formation via changes in expression of matrix metalloproteases, such as, MT1-MMP (membrane type metalloprotease), and increased synthesis of matrix molecules. Several studies have suggested an association between MT1-MMP and integrins, which are known to influence cell shape. Thus, the objectives of this study were to determine the effect of compressive mechanical stimulation on cell shape and the role of integrins and MT1-MMP in mediating these changes and influencing matrix accumulation. Bovine articular chondrocytes were grown on the surface of a porous ceramic substrate for 72 h and then cyclically compressed for 30 min. Scanning electron microscopy and morphometric analysis demonstrated that compression induced a rapid, transient increase in chondrocyte spreading by 10 min, followed by a retraction to prestimulated size within 6 h. This was associated with increased accumulation of newly synthesized proteoglycans, as determined by quantification of radioisotope incorporation. Blocking the alpha5beta1 integrin, or its beta1 subunit, inhibited cell spreading and resulted in a partial inhibition of compression-induced increase in matrix accumulation. Knockdown of MT1-MMP expression partially inhibited cell retraction and resulted in a reduced matrix accumulation as well. These results suggest that chondrocyte spreading and retraction following cyclic compression in vitro regulates matrix accumulation. Understanding the mechanisms that regulate chondrocyte mechanotransduction may ultimately lead to the design of improved repair tissue for cartilage damage. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

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“…Our present results, taken together, precisely indicate that Src-PLCγ1-ERK1/2 is one of the important signal transduction pathways in the processes of chondrocyte proliferation and matrix synthesis induced by periodic mechanical stress. It has come to light that chondrocyte proliferation and migration function as major determinants directly affecting the quality of tissue-engineered cartilage (5,38,39). Therefore, Src-PLCγ1-ERK1/2 is one of the crucial signaling pathways that improve the quality of tissue-engineered cartilage in two different aspects under conditions of periodic mechanical stress.…”

Section: Discussionmentioning

confidence: 99%

“…These mechanical stimuli are important factors in the maintenance of normal structure and function of the articular cartilage. Periodic mechanical stress, as a special type of mechanical stimulation, can be used to advantage to simulate in vivo physiological mechanical conditions, enhancing the quality of tissue-engineered cartilage by promoting chondrocyte proliferation, migration, and matrix synthesis, which plays an important role in the repair of articular cartilage injury (2)(3)(4)(5). However, the mechanisms involved in chondrocytes to detect and respond to periodic mechanical stress have not been identified.…”

Section: Introductionmentioning

confidence: 99%

Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCγ1

Huang

Liang

Liu

et al. 2011

Braz J Med Biol Res

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Substrate architecture and fluid-induced shear stress during chondrocyte seeding: Role of α5β1 integrin

Cited by 12 publications

References 28 publications

Improved bioengineered cartilage tissue formation following cyclic compression is dependent on upregulation of MT1‐MMP

Improved bioengineered cartilage tissue formation following cyclic compression is dependent on upregulation of MT1‐MMP

Matrix accumulation by articular chondrocytes during mechanical stimulation is influenced by integrin‐mediated cell spreading

Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCγ1

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