All living organisms, from animals to single cells, adapt to environmental challenges to survive and function. Not surprisingly, exercise is the most recommended countermeasure to improve quality of life in humans afflicted with musculoskeletal disorders including osteoporosis, arthritis and obesity. In this way, lineage decisions of multipotential mesenchymal stem cells (MSC) that rejuvenate and repair tissues of mesenchymal origin (muscle, bone, cartilage and fat) are subject to control by mechanical factors. It is abundantly clear that exercise provides physiologic signals to maintain musculoskeletal health, increasing muscle tone, bone quality and decrease fatty infiltration. However, establishing causative relationships between how beneficial effect of exercise is transduced at cellular level remains elusive, thus forming the basis of our motivation to provide therapeutic solutions through careful study of mechanobiology.