Meyer EG, Buckley CT, Thorpe SD, Kelly DJ., Low oxygen tension is a more potent promoter of chondrogenic, Journal of Biomechanics, 43, 13, 2010, 2516-2523
Journal of Biomechanics 43 13
During fracture healing and microfracture treatment of cartilage defects mesenchymal
stem cells (MSCs) infiltrate the wound site, proliferate extensively and differentiate along a
cartilaginous or an osteogenic lineage in response to local environmental cues. MSCs may be
able to directly sense their mechanical environment or alternatively, the mechanical environment
could act indirectly to regulate MSC differentiation by inhibiting angiogenesis and diminishing
the supply of oxygen and other regulatory factors. Dynamic compression has been shown to
regulate chondrogenesis of MSCs. In addition, previous studies have shown that a low oxygen
environment promotes in vitro chondrogenesis of MSCs. The hypothesis of this study is that a
low oxygen environment is a more potent promoter of chondrogenic differentiation of MSCs
embedded in agarose hydrogels compared to dynamic compression. In MSC-seeded constructs
supplemented with TGF-β3, GAG and collagen accumulation was higher in low oxygen
conditions compared to normoxia. For normoxic and low oxygen culture GAG accumulation
within the agarose hydrogel was inhomogeneous, with low levels of GAG measured in the
annulus of constructs maintained in normoxic conditions. Dynamic compression did not
significantly increase GAG or collagen accumulation in normoxia. However under low oxygen
conditions, dynamic compression reduced GAG accumulation compared to free-swelling
controls, but remained higher than comparable constructs maintained in normoxic conditions.
This study demonstrates that continuous exposure to low oxygen tension is a more potent prochondrogenic
stimulus than one hr/day of dynamic compression for porcine MSCs embedded in
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