Targeting mechanotransduction pathways in osteoarthritis: a focus on the pericellular matrix

Mechanical joint loading is an essential factor in joint homeostasis but it is also the most important aetiological factor in the development of osteoarthritis (OA). Although OA has long been regarded a disease of 'wear and tear', data arising from studies over the past 10 years have put pay to a mechanical 'attrition' theory of OA and place the induction and activation of specific matrix degrading enzymes centrally in the disease process. The finding that these enzymes are induced in vivo in a mechanosensitive manner provides a clear and sensible unifying hypothesis for disease pathogenesis; namely that mechanical 'wear' actively drives the enzymes that produce 'tear'. This review focuses on recent advances in our knowledge of the molecular mechanisms by which chondrocytes (and most likely other cells of the joint) sense and respond to changes in their mechanical environment. As mechanical signals drive both beneficial responses as well as those that drive disease, modulation of specific pathways provides a choice of strategies for treating OA.