Lumican inhibits collagen deposition in tissue engineered cartilage

W Kafienah, F Cheung, TJ Sims, I Martin, S Miot, C Von Ruhland, PJ Roughley, AP Hollander

Research output: Contribution to journalArticle (Academic Journal)peer-review

17 Citations (Scopus)

Abstract

Lumican is a glycoprotein that is found in the extracellular matrix of many connective tissues, including cartilage. It is a member of the small leucine-rich repeat proteoglycans family and along with two others, decorin and fibromodulin, has the capacity to bind to fibrillar collagens and limit their growth. Cartilage tissue engineering provides a potential method for the production of three-dimensional tissue for implantation into eroded joints. Many studies have demonstrated the growth of cartilage in vitro. However in all cases, biochemical analysis of the tissue revealed a significant deficit in the collagen content. We have now tested the hypothesis that the reduced collagen accumulation in engineered cartilage is a result of over-expression of decorin, fibromodulin or lumican. We have found that the lumican gene and protein are both over-expressed in engineered compared to natural cartilage whereas this is not the case for decorin or fibromodulin. Using a small hairpin lumican antisense sequence we were able to knockdown the lumican gene and protein expression in chondrocytes being used for tissue engineering. This resulted in increased accumulation of type II collagen (the major collagen of cartilage) whilst there was no significant alteration in the proteoglycan content. Furthermore, the antisense knockdown of lumican resulted in an increase in the average collagen fibril diameter measured by transmission electron microscopy. These results suggest that lumican plays a pivotal role in the development of tissue engineered cartilage and that regulation of this protein may be important for the production of high-quality implants.
Translated title of the contributionLumican inhibits collagen deposition in tissue engineered cartilage
Original languageEnglish
Pages (from-to)526 - 534
Number of pages9
JournalMatrix Biology
Volume27
Issue number6
DOIs
Publication statusPublished - Jul 2008

Bibliographical note

Publisher: ELSEVIER

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