Targeting P2 receptors-current progress in treating musculoskeletal diseases

•Various P2 receptor knockout mice have alterations in the musculoskeletal system.•P2X receptor signalling is a novel target for cancer-induced bone pain.•P2X7 receptor agonists have pharmaceutical potential in treating osteoporosis.•ADP acts as a powerful osteolytic agent via P2Y13 signalling.•The P2Y12 receptor antagonist Clopidogrel is associated with osteoporotic fracture.

It is widely recognized that purinergic signalling, extracellular nucleotides acting at purinergic receptors, is the most primitive and ubiquitous signalling system participating in numerous biological processes in almost all tissue types. The P2 receptors, including P2X and P2Y purinoceptor subtypes, have been proposed to play important roles in the musculoskeletal systems since the early 1990s. During the past five years, significant progress in this field has been made; this review will summarize these most recent developments and highlight the pharmaceutical potential from these findings.