Hypoxia inducible factor-1alpha deficiency affects chondrogenesis of adipose-derived adult stromal cells.
Increased cartilage-related disease, poor regeneration of cartilage tissue, and limited treatment options have led to intense research in tissue engineering of cartilage. Adipose-derived adult stromal cells (ADAS) are a promising cell source for skeletal tissue engineering; understanding ADAS cellular signaling and chondrogenesis will advance cell-based therapies in cartilage repair. Chondrocytes are unique-they are continuously challenged by a hypoxic microenvironment. Hypoxia inducible factor-1-alpha (HIF-1alpha), a critical mediator of a cell's response to hypoxia, plays a significant role in chondrocyte survival, growth arrest, and differentiation. By using an established in vitro 3-dimensional micromass system, we investigated the role of HIF-1alpha in chondrogenesis. Targeted deletion of HIF-1alpha in ADAS substantially inhibited the chondrogenic pathway specifically. In marked contrast, deletion of HIF-1alpha did not affect osteogenic differentiation but enhanced adipogenic differentiation. This study demonstrates the critical and specific interplay between HIF-1alpha and chondrogenesis in vitro.
Malladi
Preeti
P
Children's Surgical Research Program, Department of Surgery, Stanford University School of Medicine, Stanford, California 94305, USA.
Xu
Yue
Y
Chiou
Michael
M
Giaccia
Amato J
AJ
Longaker
Michael T
MT
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D020219:Chondrogenesis / Q000502:physiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*
C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit