Tissue transglutaminase regulates chondrogenesis in mesenchymal stem cells on collagen type XI matrices

Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Amino Acids (Impact Factor: 3.29). 08/2011; 42(2-3):1045-53. DOI: 10.1007/s00726-011-1019-7
Source: PubMed


Tissue transglutaminase (tTG) is a multifunctional enzyme with a plethora of potential applications in regenerative medicine and tissue bioengineering. In this study, we examined the role of tTG as a regulator of chondrogenesis in human mesenchymal stem cells (MSC) using nanofibrous scaffolds coated with collagen type XI. Transient treatment of collagen type XI films and 3D scaffolds with tTG results in enhanced attachment of MSC and supports rounded cell morphology compared to the untreated matrices or those incubated in the continuous presence of tTG. Accordingly, enhanced cell aggregation and augmented chondrogenic differentiation have been observed on the collagen type XI-coated poly-(L-lactide) nanofibrous scaffolds treated with tTG prior to cell seeding. These changes implicate that MSC chondrogenesis is enhanced by the tTG-mediated modifications of the collagen matrix. For example, exogenous tTG increases resistance to collagenolysis in collagen type XI matrices by catalyzing intermolecular cross-linking, detected by a shift in the denaturation temperature. In addition, tTG auto-crosslinks to collagen type XI as detected by western blot and immunofluorescent analysis. This study identifies tTG as a novel regulator of MSC chondrogenesis further contributing to the expanding use of these cells in cartilage bioengineering.

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    • "This collagen is deposited by mesenchymal stem cells undergoing chondrogenic differentiation (Xu et al. 2008) and has been identified as a potential substrate for tissue TGases by [ 3 H]-putrescine incorporation (Kleman et al. 1995). Shanmugasundaram et al. (2011) show that TGase2-mediated crosslinking of collagen XI accompanied by autocross-linking of TGase2 protein promotes chondrogenesis in human stem cells. This study suggests an attractive alternative for enhanced cartilage formation through TGase2-mediated scaffold modifications versus genetic alteration of the cells. "

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