Biglycan: A Multivalent Proteoglycan Providing Structure and Signals

Research over the past few years has provided fascinating results indicating thatbiglycan, besides being a ubiquitous structural component of the extracellular matrix(ECM), may act as a signaling molecule. Proteolytically released from the ECM, biglycanacts as a danger signal signifying tissue stress or injury. As a ligand of innate immunityreceptors and activator of the inflammasome, biglycan stimulates multifunctionalproinflammatory signaling linking the innate to the adaptive immune response. Byclustering several types of receptors on the cell surface and orchestrating theirdownstream signaling events, biglycan is capable to autonomously trigger sterileinflammation and to potentiate the inflammatory response to microbial invasion. Besidesoperating in a broad biological context, biglycan also displays tissue-specific affinitiesto certain receptors and structural components, thereby playing a crucial role in boneformation, muscle integrity, and synapse stability at the neuromuscular junction. Thisreview attempts to provide a concise summary of recent data regarding the involvement ofbiglycan in the regulation of inflammation and the musculoskeletal system, pointing outboth a signaling and a structural role for this proteoglycan. The potential of biglycan asa novel therapeutic target or agent for the treatment of inflammatory diseases andskeletal muscular dystrophies is also addressed.