Dendritic processes of osteocytes are mechanotransducers that induce the opening of hemichannels

Osteocytes with long dendritic processes are known to sense mechanical loading, which is essential for bone remodeling. There has been a long-standing debate with regard to which part(s) of osteocyte, the cell body versus the dendritic process, acts as a mechanical sensor. To address this question experimentally, we used a transwell filter system that differentiates the cell body from the dendritic processes. Mechanical loading was applied to either the cell body or the dendrites, and the osteocyte's response was observed through connexin 43 hemichannel opening. The hemichannels located on the cell body were induced to open when mechanical loading was applied to either the dendritic processes or the cell body. However, no significant hemichannel activity in the dendrites was detected when either part of the cell was mechanically stimulated. Disruption of the glycocalyx by hyaluronidase on the dendrite side alone is sufficient to diminish a dendrite's ability to induce the opening of hemichannels on the cell body, while hyaluronidase has no such effect when applied to the cell body. Importantly, hyaluronidase treatment to the dendrite side resulted in formation of poor integrin attachments with the reduced ability of the dendrites to form integrin attachments on the underside of the transwell filter. Together, our study suggests that the glycocalyx of the osteocyte dendritic process is required for forming strong integrin attachments. These integrin attachments probably serve as the mechanotransducers that transmit the mechanical signals to the cell body leading to the opening of hemichannels, which permits rapid exchange of factors important for bone remodeling.