Back to the Future: Evaluation of the Role of Glutamate in Bone Cells

Excerpt

The recent re-examination of all things osteogenic, in particular those associated with the osteocyte, has led to a revolution in efforts to understand this long ignored cell [1]. Derived from mesenchymal progenitors and doomed to a life entrapped in the mineralized skeleton, the osteocyte has emerged as a major regulator controlling much of bone resorption and formation. If there is any truth to the concept that form follows function, then it is perhaps not surprising that the morphology of the osteocyte, with long and interconnected canaliculi reaching into virtually all aspects of the bone microenvironment, is positioned to be so important. This morphology, reminiscent of a neuron, suggested that the osteocyte was capable of transmitting signals over long distances, analogous to the nervous system. Such a suggestion led many investigators to search for neural-related molecules in osteocytes. In the late 1990s, multiple investigators identified the expression and function of the ionotropic glutamate receptor NMDA receptor (NMDAR) in osteocyte-enriched bone [2‐4], suggesting that glutamate may also act as a signaling molecule in bone and regulate bone cell metabolism. Indeed, these original studies were soon followed by others that demonstrated NMDAR and glutamate transporter expression in both osteoblasts and osteoclasts [3, 5] as well as regulation [6‐8]. …