Intensity-dependent effect of treadmill running on differentiation of rat bone marrow stromal cells

The effect of running on bone mass depends on its intensity. However, the underlying molecular mechanism that associates running intensity with bone mass is unclear. The current study examined the effects of treadmill running at different intensities on bone mass and osteogenic differentiation of bone marrow stromal cells (BMSCs) in a rat model. A total of 24 male Wistar rats were randomly divided into groups and subjected to no running (Con group), low-intensity running (LIR group), moderate-intensity running (MIR group), and high-intensity running (HIR group). Histological, immunohistochemistry and micro-CT examinations were performed on the femora harvested after 8 weeks of treadmill running. The study demonstrated that treadmill running affected trabecular bone mass in an intensity-dependent manner. In addition, such an intensity-dependent effect was also demonstrated on the osteogenic and adipogenic differentiation and proliferation of BMSCs. Furthermore, the Wnt/β-catenin signaling pathway may be involved in the running-induced increase in bone mass in rats in the MIR group. There appears to be a biomechanical ‘window’, in which running-induced strain signals can increase the number of BMSCs and progenitor cells (specific to the osteoblast lineage) causing upregulation of osteogenesis and downregulation of adipogenesis of BMSCs. This finding may provide insight into the molecular and cellular mechanisms responsible for bone homeostasis.