title: BMP2 cross-linked by transglutaminase 2 to collagen-plla scaffold promotes osteogenic differentiation in mesenchymal stem cells.
abstract: Transglutaminase 2 (TG2) was used to attach biologically-active BMP2 to collagen type I-coated poly-L-lactic acid (PLLA) nanofibrous scaffolds. Irreversibly cross-linked BMP2 retained its activity and induced Smad-dependent gene expression in cells seeded on PLLA-BMP2 scaffolds. These modified scaffolds promote osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) cultured in low-serum and growth factor free medium and support deposition of the calcified matrix and induction of the molecular osteogenic markers Runx2, osteopontin, osteonectin and bone sialoprotein. Importantly, the PLLA-BMP2 scaffolds did not support chondrogenic differentiation in hBMSCs as there was no expression of chondrogenic markers aggrecan, Sox 9, and collagen type II, and no deposition of cartilaginous glycosaminoglycan-rich matrix. Thus, TG2-mediated cross-linking of BMP2 to a scaffold is a novel approach to induce osteoblast-specific programming of hBMSCs in a spatially controlled manner.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA, kbeazley@som.umaryland.edu.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Beazley
authors.forename: Maria
authors.initials: M
authors.lastname: Nurminskaya
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D010006:Osteoblasts / Q000502:physiology*; D010012:Osteogenesis; D011091:Polyesters / Q000378:metabolism*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D054457:Tissue Scaffolds; D011503:Transglutaminases / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D011091:Polyesters; C033616:poly(lactide); D003094:Collagen; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins