Studies report osteocyte apoptosis following mechanical stimulati

Studies report osteocyte apoptosis following mechanical stimulation in the ulnar physical load model [151] and in the experimental tooth movement model in rats [130] and [152]. In addition, Aguirre et al. [153] demonstrated that osteocyte apoptosis was induced in the murine model of unloading by tail suspension. We previously reported that apoptosis of compressive force-loaded osteocytes showed the

typical histological features of nuclear condensation and fragmentation [130]. Osteocyte apoptosis occurs at sites of microdamage, where the dying osteocyte may send signals to osteoclasts for targeted removal RO4929097 in vivo of bone [154]. It was found that Bax, an proapoptotic gene product, was elevated in osteocytes immediately at the microcrack site, whereas Bcl-2, an anti-apoptotic gene product, was expressed in cells 1–2 mm away from the microcrack [154]. This suggests that damaged osteocytes send signals for bone resorption, whereas osteocytes not engaged in apoptosis are prevented from

doing so by active protective mechanisms [154]. We found significant increases in apoptosis-related gene expression, including caspase-3, -8, -9 and Bcl-2 in osteocytes during compressive force loading, indicating that both death-receptor and mitochondrial pathways were activated in osteocytes under compressive force loading [155]. In addition, others have reported that osteocyte apoptotic bodies can initiate osteoclastogenesis [156]. It is still unclear whether signals of resorption sent by dying osteocytes are the same as those sent by living osteocytes. Further investigation is necessary to elucidate the mechanism of the initiation of bone AZD5363 nmr resorption controlled by osteocytes under compressive force loading. CCN proteins induce apoptosis in some cell types

[119] and [157]. Juric et al. [157] reported that CCN1 and CCN2 synergize with FAS ligand, a TNF family member, to induce human skin fibroblast apoptosis. In human breast cancer cells [119] and aortic smooth-muscle cells [158], CTGF/CCN2 induces apoptosis by decreasing Bcl-2 protein expression and the activation of caspase 3, respectively. In contrast, CTGF/CCN2 inhibits apoptosis in human rhabdomyosarcoma cells [159]. However, in osteocytes, it was previously unclear whether CCN2 induced osteocyte apoptosis. Cell press We showed that in the mouse experimental tooth movement model, CCN2 mRNA expression in osteocytes increased on the pressured side of alveolar bone, which induced osteocyte apoptosis and osteoclastic bone resorption [130]. Furthermore, recently we demonstrated that recombinant human (rh)CCN2 induced osteocyte apoptosis in primary chick osteocytes in culture [155]. Thus, we speculate that the enhanced expression of CCN2 after compressive force loading could be related to osteocyte apoptosis, which might be an important phenomenon in the dynamic responses of these cells to mechanical stimuli to induce bone resorption.

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