Use of staurosporine, an actin-modifying agent, to enhance fibrochondrocyte matrix gene expression and synthesis. Cell Tissue Res 2008 Dec;334(3):469-76
Date
11/06/2008Pubmed ID
18985390DOI
10.1007/s00441-008-0705-6Scopus ID
2-s2.0-59449097790 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Modulation of the actin cytoskeleton in chondrocytes has been used to prevent or reverse dedifferentiation and to enhance protein synthesis. We have hypothesized that an actin-modifying agent, staurosporine, could be used with fibrochondrocytes to increase the gene expression and synthesis of critical fibrocartilage proteins. A range of concentrations (0.1-100 nM) was applied to fibrochondrocytes in monolayer and evaluated after 24 h and after 4 days. High-dose staurosporine treatment (10-100 nM) increased cartilage oligomeric matrix protein 60- to 500-fold and aggrecan gene expression two-fold. This effective range of staurosporine was then applied to scaffoldless tissue-engineered fibrochondrocyte constructs for 4 weeks. Whereas glycosaminoglycan synthesis was not affected, collagen content doubled, from 27.6 +/- 8.8 microg in the untreated constructs to 55.2 +/- 12.2 microg per construct with 100 nM treatment. When analyzed for specific collagens, the 10-nM group showed a significant increase in collagen type I content, whereas collagen type II was unaffected. A concomitant dose-dependent reduction was noted in construct contraction, reflecting the actin-disrupting action of staurosporine. Thus, staurosporine increases the gene expression for important matrix proteins and can be used to enhance matrix production and reduce contraction in tissue-engineered fibrocartilage constructs.
Author List
Hoben GM, Athanasiou KAAuthor
Gwendolyn M B Hoben MD Assistant Professor in the Plastic Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ActinsAnimals
Cattle
Chondrocytes
Collagen
Extracellular Matrix Proteins
Gene Expression Regulation
Immunohistochemistry
Male
Phalloidine
Staining and Labeling
Staurosporine
Time Factors
Tissue Engineering
