Inhibitory effects of beta-tricalciumphosphate wear particles on osteocytes via apoptotic response and Akt inactivation

详细信息	查看全文 | 推荐本文 |

• 作者：Yun Zhang^a ; ^b ; ^{yunzhang1976@gmail.com} ; Ming Yan^c ; Aiyue Yu^a ; Hongjiao Mao^a ; Jinping Zhang^a
• 关键词：Wear particles ; Osteocytes ; Apoptosis ; Akt signaling
• 刊名：Toxicology
• 出版年：2012
• 期刊代码：47_0300483x
• 类别：pha
• 出版时间：16 July, 2012
• 卷：297
• 期：1-3
• 页码：57-67
• 文件大小：2026 K

摘要

Wear debris-induced osteolysis, a major contributing factor of orthopedic implant aseptic loosening, affects long-term survival of orthopedic prostheses following joint replacement and revision surgery. Pathogenic effects of wear debris on various cell types including macrophages/monocytes, osteoblasts, and osteoclasts have been well studied. However, the interactions between wear debris particles and osteocytes, which make up over 90%of all bone cells, have not been clearly illustrated. Here, we explored the biological effects of endotoxin-free beta-tricalciumphosphate (尾-TCP) wear particles with the average diameter of 1.997 渭m (range 1.3-3.2 渭m) on osteocytes in vitro. Our results showed that 24 h or 48 h incubation of 尾-TCP particles dose-dependently inhibited cell viability of osteocytes MLO-Y4. Alternatively, 尾-TCP particles treatment for 24 h significantly increased the osteocytic marker SOST/sclerostin mRNA expression and the release of inflammatory cytokines including TNF-伪 and IL-1尾 into the culture media, but decreased the mRNA expression of another osteocytic marker dentin matrix protein-1 (DMP-1). Furthermore, these osteocytes dysfunctions were accompanied by F-actin disassembly, cell apoptosis, sustained enhancement of intracellular reactive oxygen species (ROS) and mitochondrial injury upon 尾-TCP particles stimulation. In addition, 尾-TCP particles also caused Akt inactivation at Ser473 resides with a dose- and time-dependent pattern. Taken together, 尾-TCP wear particles could cause osteocytes dysfunctions, which may be mediated by apoptotic death and Akt inactivation in MLO-Y4 cells. These findings strongly suggest that osteocytes may play an important role in the 尾-TCP wear particles-induced osteolysis, and provide valuable insights for understanding the molecular mechanisms of osteocytes death involved in tissue damage during bone cement and intolerance of cemented prostheses.