Bone Morphogenetic Protein-2 Causes Commitment and Differentiation in C3Hl0T1/2 and 3T3 Cells

Abstract

C3H10T1/2 cells are an established mesenchymal stem cell line which can differentiate into muscle, fat and cartilage cells when treated with azacytidine. Bone morphogenetic protein-2 (BMP-2) caused a dose dependent differentiation of these cells into fat, cartilage and bone cells-low concentrations favoring adipocytes and high concentrations chondrocytes and osteoblasts. The differentiated phenotypes were stable in the absence of BMP-2. Furthermore, the addition of other growth factors during the differentiation process altered the frequency of the differentiated colony formation. Transfection of the C3H10T1/2 cells with a BMP-2 cDNA also induced a phenotypic change from the parental fibroblast to adipocytes and osteoblasts. Our results in this model system indicate that a single protein factor can cause differentiation of a stem cell line to multiple phenotypes, that phenotypes induced can be regulated by factor concentration, and that other factors can also influence BMP-2 induced differentiation.

Bone regeneration in critical size defects by cell-mediated BMP-2 gene transfer: a comparison of adenoviral vectors and liposomes

“…This has also been documented in previous studies on a mesenchymal cell line. 21,22 A combination of bone marrow transplantation and application of rhBMP-2 also suggested a synergistic effect on bone healing. 32 This potential of BMP-2-producing BMSC might be the main reason for our favourable results in vivo obtained even with the less efficient liposome-mediated gene transfer.…”

“…Previous studies showed that transfection of BMP-2-cDNA into a mesenchymal cell line stimulated the osteogenic pathway via autocrine and paracrine mechanisms in vitro and in vivo. 21,22 In this study, we investigated the transplantation of BMP-2-producing primary rat bone marrow stromal cells (BMSC), modified by either liposomemediated or adenoviral BMP-2 gene transfer, into bone defects in vitro and in vivo and compared the two approaches with respect to the efficacy of bone regeneration.…”

A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs

“…However, it has also been demonstrated that BMPs have pro‐adipogenic effects 8. For example, BMP2/4 can induce adipocytic lineage commitment of MSCs through activation of p38 Smad/MAPK signalling 9, 10, 11. In addition, other side effects, such as increased cancer risk related to higher BMP doses, have also been reported 12.…”

Efficacy of Simvastatin in Bone Regeneration After Surgical Removal of Mandibular Third Molars: A Clinical Pilot Study

“…Wang et al [2] showed that BMP-2 causes differentiation of a multipotential stem cell line into osteoblast-like cells. To discover small molecules that induce BMP-2, Mundy et al [3] examined more than 30,000 compounds from a collection of natural products and tested the effects of compounds on the expression of the BMP-2 gene.…”