Lumican inhibits collagen deposition in tissue engineered cartilage

Kafienah, Wáel; Cheung, Frank L.; Sims, Trevor J.; Martin, Ivan; Miot, Sylvie; Ruhland, Christopher Von; Roughley, Peter J.; Hollander, Anthony P.

doi:10.1016/j.matbio.2008.04.002

Cited by 22 publications

(21 citation statements)

References 38 publications

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“…The decrease in decorin evident by IHC staining shown immediately post-treatment in the present study may allow larger diameter collagen fibers to be formed or previously blocked interactions between neighboring collagens to take place, both of which could lead to a more functional collagen network and increased tensile properties. This proposition is similar to a recently described mechanism whereby selective knockdown of the small proteoglycan lumican led to increased collagen deposition and fibril diameter in a polyglycolic acid scaffold based approach to cartilage engineering employing bovine nasal chondrocytes 11. In addition to decorin and lumican, aggrecan and biglycan have a role in the observed changes.…”

Section: Discussionsupporting

confidence: 83%

Effects of multiple chondroitinase ABC applications on tissue engineered articular cartilage

Natoli

Responte

et al. 2009

Journal Orthopaedic Research

111

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Increasing tensile properties and collagen content is a recognized need in articular cartilage tissue engineering. This study tested the hypothesis that multiple applications of chondroitinase ABC (C-ABC), a glycosaminoglycan (GAG) degrading enzyme, could increase construct tensile properties in a scaffold-less approach for articular cartilage tissue engineering. Developing constructs were treated with C-ABC at 2 weeks, 4 weeks, or both 2 and 4 weeks. At 4 and 6 weeks, construct sulfated GAG composition, collagen composition, and compressive and tensile biomechanical properties were assessed, along with immunohistochemistry (IHC) for collagens type I, II, and VI, and the proteoglycan decorin. At 6 weeks, the tensile modulus and ultimate tensile strength of the group treated at both 2 and 4 weeks were significantly increased over controls by 78% and 64%, reaching values of 3.4 and 1.4 MPa, respectively. Collagen concentration also increased 43%. Further, groups treated at either 2 weeks or 4 weeks alone also had increased tensile stiffness compared to controls. Surprisingly, though GAG was depleted in the treated groups, by 6 weeks there were no significant differences in compressive stiffness. IHC showed abundant collagen type II and VI in all groups, with no collagen type I. Further, decorin staining was reduced following C-ABC treatment, but returned during subsequent culture. The results support the use of C-ABC in cartilage tissue engineering for increasing tensile properties.

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Section: Discussionsupporting

confidence: 83%

Effects of multiple chondroitinase ABC applications on tissue engineered articular cartilage

Natoli

Responte

et al. 2009

Journal Orthopaedic Research

111

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“…Developing an effective in vitro method for cartilage formation could provide a platform technology for investigating novel regeneration strategies, studying cartilage pathogenesis and examining cartilage development. However, numerous problems, including chondrocyte de-differentiation [1] and difficulty in reproducing the cartilage matrix [2][3][4][5] have hindered the development of effective in vitro cartilage growth models.…”

Section: Introductionmentioning

confidence: 99%

Identification of potential biophysical and molecular signalling mechanisms underlying hyaluronic acid enhancement of cartilage formation

Responte

Natoli

Athanasiou

2012

J. R. Soc. Interface.

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This study determined the effects of exogenous hyaluronic acid (HA) on the biomechanical and biochemical properties of self-assembled bovine chondrocytes, and investigated biophysical and genetic mechanisms underlying these effects. The effects of HA commencement time, concentration, application duration and molecular weight were examined using histology, biomechanics and biochemistry. Additionally, the effects of HA application on sulphated glycosaminoglycan (GAG) retention were assessed. To investigate the influence of HA on gene expression, microarray analysis was conducted. HA treatment of developing neocartilage increased compressive stiffness onefold and increased sulphated GAG content by 35 per cent. These effects were dependent on HA molecular weight, concentration and application commencement time. Additionally, applying HA increased sulphated GAG retention within self-assembled neotissue. HA administration also upregulated 503 genes, including multiple genes associated with TGF-b1 signalling. Increased sulphated GAG retention indicated that HA could enhance compressive stiffness by increasing the osmotic pressure that negatively charged GAGs create. The gene expression data demonstrate that HA treatment differentially regulates genes related to TGF-b1 signalling, revealing a potential mechanism for altering matrix composition. These results illustrate the potential use of HA to improve cartilage regeneration efforts and better understand cartilage development.

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“…Suppression of collagen type I may, therefore, help in preventing fibrogenesis while improving the hyaline features of the newly synthesized ECM. Interestingly, other ECM proteins have been targeted to improve the quality of neocartilage produced by chondrocytes and hMSCs, i.e., decorin [78], lumican [79], and asporin [80].…”

Section: Silencing Of Matrix and Secreted Proteinsmentioning

confidence: 99%

Emerging potential of gene silencing approaches targeting anti-chondrogenic factors for cell-based cartilage repair

Lolli

Penolazzi

Narcisi

et al. 2017

Cell. Mol. Life Sci.

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The field of cartilage repair has exponentially been growing over the past decade. Here, we discuss the possibility to achieve satisfactory regeneration of articular cartilage by means of human mesenchymal stem cells (hMSCs) depleted of anti-chondrogenic factors and implanted in the site of injury. Different types of molecules including transcription factors, transcriptional co-regulators, secreted proteins, and microRNAs have recently been identified as negative modulators of chondroprogenitor differentiation and chondrocyte function. We review the current knowledge about these molecules as potential targets for gene knockdown strategies using RNA interference (RNAi) tools that allow the specific suppression of gene function. The critical issues regarding the optimization of the gene silencing approach as well as the delivery strategies are discussed. We anticipate that further development of these techniques will lead to the generation of implantable hMSCs with enhanced potential to regenerate articular cartilage damaged by injury, disease, or aging.

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Lumican inhibits collagen deposition in tissue engineered cartilage

Cited by 22 publications

References 38 publications

Effects of multiple chondroitinase ABC applications on tissue engineered articular cartilage

Effects of multiple chondroitinase ABC applications on tissue engineered articular cartilage

Identification of potential biophysical and molecular signalling mechanisms underlying hyaluronic acid enhancement of cartilage formation

Emerging potential of gene silencing approaches targeting anti-chondrogenic factors for cell-based cartilage repair

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