TNAP, TrAP, ecto‐purinergic signaling, and bone remodeling

AbstractBone remodeling is a process of continuous resorption and formation/mineralization carried out by osteoclasts and osteoblasts, which, along with osteocytes, comprise the bone multicellular unit (BMU). A key component of the BMU is the bone remodeling compartment (BRC), isolated from the marrow by a canopy of osteoblast‐like lining cells. Although much progress has been made regarding the cytokine‐dependent and hormonal regulation of bone remodeling, less attention has been placed on the role of extracellular pH (pHe). Osteoclastic bone resorption occurs at acidic pHe. Furthermore, osteoclasts can be regarded as epithelial‐like cells, due to their polarized structure and ability to form a seal against bone, isolating the lacunar space. The major ecto‐phosphatases of osteoclasts and osteoblasts, acid and alkaline phosphatases, both have ATPase activity with pH optima several units different from neutrality. Furthermore, osteoclasts and osteoblasts express plasma membrane purinergic P2 receptors that, upon activation by ATP, accelerate bone osteoclast resorption and impair osteoblast mineralization. We hypothesize that these ecto‐phosphatases help regulate [ATP]e and localized