It has been shown that MEPE expression is upregulated in a time-dependent Etoposide order fashion in alveolar osteocytes in response to mechanical loading applied by orthodontic tooth movement [115], and MEPE expression is enhanced in osteocytes subjected to mechanical loading in vitro [116]. Dentin matrix protein 1 (DMP1) is another molecule that seems to be highly expressed in osteocytes compared to other cells types [117] and [118]. A potential role of DMP1 in osteocytes may be related to hydroxyapatite formation. DMP1 is specifically expressed along and in the canaliculi of osteocytes within the bone matrix

[117]. The canaliculi and lacunae in bones of DMP1-null mice have a compromised structure, which can have implications for the amplification of load signals to the osteocytes [119]. DMP1 expression increases 2 to 3-fold in osteocytes of the mouse ulna at 24 h after a single 2.4 N load for 30 s at 2 Hz [120]. Phex gene expression is also increased in response to mechanical loading [120]. The precise function of Phex is unclear but it clearly plays a role in phosphate homeostasis and bone mineralization. Signaling molecules produced by mechanically-loaded osteocytes modulate the recruitment and activity of osteoblasts and/or osteoclasts.

Osteoblast recruitment and activity can be stimulated Pexidartinib by prostaglandins and Wnts [121], [122] and [123]. Fluid flow-subjected osteocytes stimulate alkaline phosphatase activity in osteoblasts [124]. NO also has an anabolic effect on osteoblast activity. Osteoclast activity seems to be inhibited by NO produced in osteocytes [49]. MLO-Y4 osteocytes also produce M-CSF, RANKL, and OPG, and are thereby able to actively promote osteoclast formation and activity under static culture conditions. The promotion of osteoclast formation depends on cell–cell contact, possibly Palbociclib in vivo due to the requirement of cell-bound RANKL [125] and [126]. Indeed it has been shown recently that bone mass in adult mice is determined by RANKL produced by osteocytes rather than osteoblasts [15] and [16]. In bone, skeletal homeostasis is achieved

by local osteoclast-mediated degradation of the bone matrix and osteoblast-mediated formation of new bone matrix without compromising the overall architecture and anatomy of bone. This is achieved in accordance with the external mechanical loading conditions to which the bone is subjected. Osteocytes play a central role in this remodeling process by sensing the external mechanical loads and then transmitting the information to the effector cells, the osteoblasts and/or the osteoclasts, which then maintain the skeletal homeostasis. All authors have no conflicts of interest. “
“Bone has long been known to be responsive to mechanical loading. The ability of bone to functionally adapt to forces was discovered in the late 19th and early 20th centuries [1], [2], [3], [4] and [5].