Generation and function of osteocyte dendritic processes.

Osteocytes in vivo possess a distinctive morphology – that of dendricity – connecting osteocyte to osteocyte creating the osteocyte syncytium and also connecting osteocytes with cells on the bone surface (see Figure 1). It is thought that bone fluid surrounding the dendrite within the canaliculi is responsible for the transmission of mechanical strain through fluid flow shear stress. Dendrites may be essential for osteocyte function, viability, and response to load. The cell processes of osteocytes are connected with each other via gap junctions, thereby allowing direct cell-to-cell coupling. Osteocytes and MLO-Y4 osteocyte-like cells express large amounts of Connexin 43, the component of gap junctions. But as these cells are only in contact through the tips of their dendritic processes, this raises the question, what is the function of Cx 43 located on the rest of the cell membrane? Recently it has been shown that connexins can complex and function in the form of un-apposed halves of gap junction channels called hemichannels. These channels are localized at the cell surface, independent of physical contact with adjacent cells. Recently evidence of functional hemichannels formed by Cx43 has been reported in neural progenitors and neurons, astrocytes, heart, and especially, osteoblasts and osteocytes. The opening of hemichannels appears to provide a mechanism for ATP and NAD release, which raises intracellular Ca levels and promotes Ca wave propagation in astrocytes, bone cells, epithelial cells, and outer retina. Hemichannels expressed in bone cells such as MLO-Y4 cells appear to function as essential transducers of the anti-apoptotic effects of bisphosphonates and act as a portal for the extracellular release of PGE2 in osteocytes upon exposure to fluid flow shear stress. Therefore, in osteocytes, gap junctions at the tip of dendrites appear to mediate a form of intracellular communication and J Musculoskelet Neuronal Interact 2005; 5(4):321-324