Amino Acids

, Volume 42, Issue 2, pp 1045–1053

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

  • Shobana Shanmugasundaram
  • Sheila Logan-Mauney
  • Kaitlin Burgos
  • Maria Nurminskaya
Original Article

DOI: 10.1007/s00726-011-1019-7

Cite this article as:
Shanmugasundaram, S., Logan-Mauney, S., Burgos, K. et al. Amino Acids (2012) 42: 1045. doi:10.1007/s00726-011-1019-7

Abstract

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.

Keywords

TransglutaminaseCollagen type XIAdult mesenchymal stem cellsTissue engineeringCartilage

Abbreviations

BSA

Bovine serum albumin

Ca2+

Calcium

CO2

Carbon dioxide

cont-tTG

Collagen type XI films continuously treated with tTG

pre-TG

Collagen type XI films pre-treated with tTG

DSC

Differential scanning calorimetry

DMEM

Dulbecco’s modified eagle medium

EDTA

Ethylenediaminetetraacetic acid

MSC

Human mesenchymal stem cells

HCl

Hydrochloric acid

PFA

Paraformaldehyde

PBS

Phosphate buffered saline

PLLA-coll XI

PLLA scaffold coated with collagen type XI

coll XI-pre tTG

PLLA-coll XI pre-treated with tTG

coll XI-cont tTG

PLLA-coll XI in the continuous presence of tTG

PLLA

Poly (L-lactide)

GAG

Sulphated glycosaminoglycan

3D

Three- dimensional

tTG

Tissue transglutaminase

2D

Two-dimensional

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Shobana Shanmugasundaram
    • 1
  • Sheila Logan-Mauney
    • 2
  • Kaitlin Burgos
    • 3
  • Maria Nurminskaya
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Maryland School of MedicineBaltimoreUSA
  2. 2.Department of Anatomy and Cell BiologyTufts University School of MedicineBostonUSA
  3. 3.Department of BiologyTowson UniversityTowsonUSA