The role of CCN2 will be discussed in more detail in later sections. Additional osteocyte selective markers, such as osteopontin (OPN) [28], dentin matrix protein 1 (DMP1) [70] and [71], osteoblast/osteocyte

factor 45 (OF45, also called MEPE) [72] and E11/gp38 [73], are also regulated by mechanical loading. Among the non-collagenous bone matrix proteins, OPN was suggested to have a role in bone remodeling by mediating osteoclast attachment. In support of this, we found that the expression level of OPN in osteocytes located in pressure-loaded bone is increased in the process of experimental bone resorption stimulated by mechanical stress during experimental tooth movement [29]. Studies show that the DMP1 gene is also activated within a few hours in response to mechanical loading in osteocytes during the BGB324 in vivo tooth movement model [70]. OF45 [72], a novel, bone-specific extracellular matrix protein, is tightly linked to mineralization and bone formation. Mouse OF45 is similar to its rat ortholog in that its expression is increased during mineralization in osteoblast cultures and within

embedded osteocytes. Osteoclastogenesis and bone resorption in ex vivo cultures, however, are unaffected by OF45 mutation in a targeted mouse line deficient in OF45 [72]. From these results, it was concluded that OF45 plays an inhibitory role in bone formation in the mouse [72]. E11/gp38, a membrane protein that is osteocyte-selective and thought to play a role see more in dendrite elongation, is also activated within 4 h after a mechanical load, not only in osteocytes near the bone surface, but also in those deeply embedded in the bone [73]. Growth factors and cytokines dramatically affect the proliferation and differentiation of cells that express their receptors. Insulin-like growth factor-1 (IGF-1) is a cytokine that stimulates collagen and DNA synthesis in osteogenic cells and its action results in an increase in bone formation in vivo [74]. Indeed, one study showed that IGF-1 mRNA expression is increased in osteocytes of the rat caudal vertebra by mechanical

loading within 6 h [75]. Furthermore, the role of IGF-1 in the translation of mechanical stimuli into bone formation locally in rat tibiae has been linked to osteocytes [76]. However, further Oxalosuccinic acid study is required to understand the role of IGF-1 produced by osteocytes responding to mechanical stress. The osteocyte-specific marker, sclerostin, is produced by osteocytes and is the Wnt signaling antagonist encoded by the Sost gene [77]. Sclerostin is decreased in response to anabolic loading [78]. In mechanical loading experiments of transgenic mice, in which they had been engineered to maintain high levels of Sost/sclerostin expression, it was found that the down-regulation of Sost/sclerostin in osteocytes is a obligatory step in the mechanotransduction cascade that activates Wnt signaling to direct osteogenesis to where bone is structurally needed [78].