GLAST expression was originally found in the central nervous system, and GLAST plays an important role in neurotransmission. Since glutamate signaling is involved in bone [92] and periodontal metabolism [18], the amino acid transporter could function

as a mechanosensing molecule in osteocytes. Loading-induced changes in the expression of transcription factors can affect the transcription of multiple downstream genes. c-fos is a cellular proto-oncogene belonging Selleck ABT888 to the immediate early response group of transcription factors that responds to mechanical stress in bone [93] and osteoblasts [94]. The c-fos gene product acts as a transcription factor, AP1, by forming a complex with c-JUN; this, in turn, governs the transcription of numerous downstream genes, including those involved in differentiation, proliferation [95], and apoptosis [95]. An increase in c-fos mRNA in osteocytes of the compressed caudal vertebrae has been demonstrated by in situ hybridization within 2 h after mechanical loading [75]. NO and prostaglandins

are two anabolic signals in osteocytes that are released within seconds in response to mechanical strain [96]. NO is a short-lived free radical that inhibits resorption and promotes bone formation [96]. The inhibition of the nitric oxide synthetase can abolish the loading-induced increase in prostaglandin ABT-263 datasheet E2 [97], and the prostaglandin inhibitor, indomethacin,

can block loading-induced new bone formation in vivo [98]. These findings suggest that osteocytes are the primary source of these load-induced prostaglandins in bone. Primary cilia are solitary, immotile, microtubule-based organelles that grow from the centrosome and project from the cell surface in many vertebrate tissues [99] and [104], including bone [100] and [101]. Single cilia are present on primary bone cells, and on osteoblastic and osteocytic cell lines. Protein kinase D (PKD)-1 and PKD2 are components of cilia with over known mechanosensory functions in the kidney that might also play a role in normal bone structure [101]. Malone et al. [102] have shown that reducing the number of cilia reduces the induction of OPN in MC3T3-E1 cells, the induction of prostaglandin in both MC3T3-E1 and MLO-Y4 cells, and the increase in COX2 and RANKL/OPG ratio in MLO-Y4 in response to fluid shear stress. Non-collagenous matrix proteins (NCPs) have multiple functions in bone cells, including the regulation of collagen fibril mineralization [103] and modulation of cell division, migration, differentiation and maturation [104]. Among them, OPN, originally purified from bone, is a sialic acid-rich 44 KD phosphorylated glycoprotein that contains an Arg-Gly-Asp (RGD) adhesion motif [105] and promotes adhesion and spreading of mesenchymal cells, fibroblasts, and osteoblast-like osteosarcoma cells.