Intercellular communication via gap junction channels between chondrocytes and bone cells

Cell-to-cell communication between bone, cartilage and the synovial membrane is not fully understood and it is only attributed to the diffusion of substances through the extracellular space or synovial fluid. In this study, we found for the first time that primary bone cells (BCs) including osteocytes, synovial cells (SCs) and chondrocytes (CHs) are able to establish cellular contacts and to couple through gap junction (GJ) channels with connexin43 (Cx43) being dominant. Transwell co-culture and identification by mass spectrometry revealed the exchange of essential amino acids, peptides and proteins including calnexin, calreticulin or CD44 antigen between contacting SCs, BCs and CHs. These results reveal that CHs, SCs and BCs are able to establish intercellular connections and to communicate through GJ channels, which provide a selective signalling route by the direct exchange of potent signalling molecules and metabolites. •Evidence of biomechanical and molecular signalling between cartilage, subchondral bone and synovial tissue have raised the concept of molecular crosstalk between tissues in the joint.•Chondrocytes, bone cells and synovial cells are able to establish cellular connections and communicate with another via contact between membrane-bound cell surface molecules and gap junction channels mainly formed by connexin43.•Gap junctions between chondrocytes and bone cells can synchronize electrical activity (electrical signals) and may enable metabolic coupling.•The discovery of such communication has potential implications on the mechanisms that regulate the interactions of these cells in health and diseases such as osteoarthritis or rheumatoid arthritis, which involve altered expression of connexin43.