Many physicians and physical therapists are daunted by the intricacies of mechanotherapy.1 Unlike drug prescription in which doses are relatively straightforward to calculate, most physicians who use exercise in their clinical armament recognise that a responsive, artful approach is demanded by the great variability in tissue responses, which are encountered clinically. The purpose of this editorial is to highlight how the response to mechanical loading and unloading follows key biological principles. We address the following question: can advances in basic science help guide the clinician's approach to chronic connective tissue conditions?

Connective tissues of the musculoskeletal system (eg, bones, tendons, ligaments, cartilage, menisci, muscles) are a diverse family of tissues essential for movement and mobility. Like most families, they share some distinctive features: they are matrix-rich tissues with relatively few cells that function well in mechanically active environments. This is despite the fact that their environments can be quite varied – some tissues work in high-stress environments while others function in lower-stress environments. In addition, some tissues are subjected to mechanical loading that is compressive (eg, cartilage, menisci, bone), others experience shear stress (eg, bone) and still others function in primarily tensile loading environments (eg, muscles, tendons, ligaments).

Cells in the different tissues respond to mechanical cues (mechanotransduction/mechanobiology).1 They also respond to biological cues from the endocrine system and to molecules produced locally in paracrine (between cells) or autocrine (a single cell produces and responds to the mediators) fashion (discussed by Zernicke et al2 and many others). This combination of biological and mechanical cues contributes to the metabolic set point for cells in these tissues and determines the anabolic (synthesis)/catabolic (degradation) balance in the various tissues (figure 1). In most tissues, this balance appears to be regulated at the …