Low Oxygen Tension is a More Potent Regulator of Chondrogenic Differentiation Than Dynamic Compression for Bone Marrow Derived Mesenchymal Stem Cells

Introduction In fracture healing 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. The mechanical environment within a fracture callus may regulate endochondral ossification during fracture healing in one of two ways. Firstly, the biophysical stimuli, such as dynamic compression, could directly promote chondrogenic differentiation of MSCs. Secondly, by preventing neo-vascularization mechanical loading could indirectly promote chondrogenesis by creating a local hypoxic environment in the defect. The process of endochondral ossification has been proposed as an alternative strategy for bone tissue engineering. Understanding how environmental factors regulate this process will be critical to realizing the potential of this approach. The hypothesis of this study is that oxygen tension is a more potent regulator of chondrogenic differentiation of MSCs compared to dynamic compression.