title: Inhibitory effects of β-tricalciumphosphate wear particles on osteocytes via apoptotic response and Akt inactivation.
abstract: 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 (β-TCP) wear particles with the average diameter of 1.997 μm (range 1.3-3.2 μm) on osteocytes in vitro. Our results showed that 24 h or 48 h incubation of β-TCP particles dose-dependently inhibited cell viability of osteocytes MLO-Y4. Alternatively, β-TCP particles treatment for 24 h significantly increased the osteocytic marker SOST/sclerostin mRNA expression and the release of inflammatory cytokines including TNF-α and IL-1β 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 β-TCP particles stimulation. In addition, β-TCP particles also caused Akt inactivation at Ser473 resides with a dose- and time-dependent pattern. Taken together, β-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 β-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.
authors.affiliation: College of Medicine, Shaoxing University, Huancheng West Road 508, Shaoxing 312000, PR China. yunzhang1976@gmail.com
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Aiyue
authors.initials: A
authors.lastname: Yu
authors.forename: Hongjiao
authors.initials: H
authors.lastname: Mao
authors.forename: Jinping
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001672:Biocompatible Materials / Q000633:toxicity; D002130:Calcium Phosphates / Q000633:toxicity*; D002478:Cells, Cultured; D006801:Humans; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010014:Osteolysis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats
chemical_list: D051017:Apoptosis Regulatory Proteins; D001672:Biocompatible Materials; D002130:Calcium Phosphates; C485817:beta-tricalcium phosphate; D051057:Proto-Oncogene Proteins c-akt