The effects of BMP6 overexpression on adipose stem cell chondrogenesis: Interactions with dexamethasone and exogenous growth factors.

Published

Journal Article

Adipose-derived stem cells (ASCs) are multipotent progenitors that can be chondrogenically induced by growth factors such as bone morphogenetic protein 6 (BMP-6). We hypothesized that nonviral transfection of a BMP-6 construct (pcDNA3-BMP6) would induce chondrogenic differentiation of ASCs encapsulated in alginate beads and that differentiation would be enhanced by the presence of the synthetic glucocorticoid dexamethasone (DEX) or the combination of epidermal growth factor (EGF), fibroblast growth factor-2 (FGF-2), and transforming growth factor beta-1 (TGF-beta1), collectively termed expansion factors (EFs). Chondrogenesis was assessed using quantitative real-time polymerase chain reaction for types I, II, and X collagen, aggrecan, and BMP6. Immunohistochemistry was performed with antibodies for types I, II, and X collagen and chondroitin-4-sulfate. BMP6 overexpression alone induced a moderate chondrogenic response. The inclusion of EFs promoted robust type II collagen expression but also increased type I and X collagen deposition, consistent with a hypertrophic chondrocyte phenotype. Early gene expression data indicated that DEX was synergistic with BMP-6 for chondrogenesis, but immunohistochemistry at 28 days showed that DEX reduced glycosaminoglycan accumulation. These results suggest that chondrogenic differentiation of ASCs depends on complex interactions among various growth factors and media supplements, as well as the concentration and duration of growth factor exposure.

Full Text

Cited Authors

  • Diekman, BO; Estes, BT; Guilak, F

Published Date

  • June 2010

Published In

Volume / Issue

  • 93 / 3

Start / End Page

  • 994 - 1003

PubMed ID

  • 19722282

Pubmed Central ID

  • 19722282

Electronic International Standard Serial Number (EISSN)

  • 1552-4965

International Standard Serial Number (ISSN)

  • 1549-3296

Digital Object Identifier (DOI)

  • 10.1002/jbm.a.32589

Language

  • eng