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

被引:44
作者
Diekman, Brian O. [1 ,2 ]
Estes, Bradley T. [1 ,2 ]
Guilak, Farshid [1 ,2 ]
机构
[1] Duke Univ, Med Ctr, Dept Surg, Div Orthopaed Surg,Orthopaed Res Labs, Durham, NC 27710 USA
[2] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA
关键词
adult stem cells; chondrogenesis; tissue engineering; bone-morphogenetic protein 6; dexamethasone; MESENCHYMAL PROGENITOR CELLS; ARTICULAR-CARTILAGE; IN-VITRO; STROMAL CELLS; BONE-MARROW; CHONDROCYTIC DIFFERENTIATION; TRIAMCINOLONE ACETONIDE; TISSUE; EXPRESSION; METHYLPREDNISOLONE;
D O I
10.1002/jbm.a.32589
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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-beta 1), 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. (C) 2009 Wiley Periodicals, Inc. J Biomed Mater Res 93A: 994-1003, 2010
引用
收藏
页码:994 / 1003
页数:10
相关论文
共 41 条
[1]   Yield of human adipose-derived adult stem cells from liposuction aspirates [J].
Aust, L ;
Devlin, B ;
Foster, SJ ;
Halvorsen, YDC ;
Hicok, K ;
du Laney, T ;
Sen, A ;
Willingmyre, GD ;
Gimble, JM .
CYTOTHERAPY, 2004, 6 (01) :7-14
[2]   Effects of transforming growth factor β1 and dexamethasone on the growth and chondrogenic differentiation of adipose-derived stromal cells [J].
Awad, HA ;
Halvorsen, YDC ;
Gimble, JM ;
Guilak, F .
TISSUE ENGINEERING, 2003, 9 (06) :1301-1312
[3]   Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds [J].
Awad, HA ;
Wickham, MQ ;
Leddy, HA ;
Gimble, JM ;
Guilak, F .
BIOMATERIALS, 2004, 25 (16) :3211-3222
[4]   ALTERATION OF RABBIT ARTICULAR-CARTILAGE BY INTRA-ARTICULAR INJECTIONS OF GLUCOCORTICOIDS [J].
BEHRENS, F ;
SHEPARD, N ;
MITCHELL, N .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 1975, A 57 (01) :70-76
[5]   Chondrocytic differentiation of human adipose-derived adult stem cells in elastin-like polypeptide [J].
Betre, H ;
Ong, SR ;
Guilak, F ;
Chilkoti, A ;
Fermor, B ;
Setton, LA .
BIOMATERIALS, 2006, 27 (01) :91-99
[6]   LMP-1, a LIM-domain protein, mediates BMP-6 effects on bone formation [J].
Boden, SD ;
Liu, YS ;
Hair, GA ;
Helms, JA ;
Hu, D ;
Racine, M ;
Nanes, MS ;
Titus, L .
ENDOCRINOLOGY, 1998, 139 (12) :5125-5134
[7]   Repeated intraarticular injections of triamcinolone acetonide alter cartilage matrix metabolism measured by biomarkers in synovial fluid [J].
Céleste, C ;
Ionescu, M ;
Poole, AR ;
Laverty, S .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2005, 23 (03) :602-610
[8]   Type I and II collagen regulation of chondrogenic differentiation by mesenchymal progenitor cells [J].
Chen, CW ;
Tsai, YH ;
Deng, WP ;
Shih, SN ;
Fang, CL ;
Burch, JG ;
Chen, WH ;
Lai, WF .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2005, 23 (02) :446-453
[9]   Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells [J].
Chiou, M ;
Xu, Y ;
Longaker, MT .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 343 (02) :644-652
[10]   Effects of dosage titration of methylprednisolone acetate and triamcinolone acetonide on interleukin-1-conditioned equine articular cartilage explants in vitro [J].
Dechant, JE ;
Baxter, GM ;
Frisbie, DD ;
Trotter, GW ;
McIlwraith, CW .
EQUINE VETERINARY JOURNAL, 2003, 35 (05) :444-450