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The effects of BMP6 overexpression on adipose stem cell chondrogenesis: Interactions with dexamethasone and exogenous growth factors
Author(s) -
Diekman Brian O.,
Estes Bradley T.,
Guilak Farshid
Publication year - 2009
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.32589
Subject(s) - chondrogenesis , chondrocyte , bone morphogenetic protein 7 , bone morphogenetic protein 6 , medicine , endocrinology , microbiology and biotechnology , bone morphogenetic protein 2 , fibroblast growth factor , aggrecan , bone morphogenetic protein , biology , chemistry , stem cell , cartilage , pathology , anatomy , biochemistry , osteoarthritis , articular cartilage , alternative medicine , receptor , gene , in vitro
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‐β1), 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. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010