Inhibition of titanium particle-induced osteoclastogenesis through inactivation of NFATc1 by VIVIT peptide.
Osteoclastogenesis induced by particulate wear debris is a major pathological factor contributing to periprosthetic osteolysis. Although the nuclear factor of activated T cells c1 (NFATc1) is known to be involved in osteoclast differentiation, its effect on osteoclastogenesis in response to wear particles remains unclear. In the present study, we investigated the role of NFATc1 in the regulation of osteoclast differentiation from bone marrow macrophages (BMMs) stimulated with titanium (Ti) particles. The results showed that Ti particles could stimulate BMMs to produce proinflammatory cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6) and differentiate into multinucleated osteoclasts in the presence of receptor activator of nuclear factor-kappaB ligand (RANKL). NFATc1 was expressed in BMMs and multinucleated cells cultured with Ti particles and RANKL. Inactivation of NFATc1 by 11R-VIVIT peptide potently impeded the Ti particle-induced osteoclastogenesis. 11R-VIVIT peptide does not have toxic effect on BMMs. Based on these data, we conclude that inactivation of NFATc1 by VIVIT peptide would provide a promising therapeutic target for the treatment of periprosthetic osteolysis.
Liu
Fengxiang
F
Department of Orthopaedic Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, PR China.
Zhu
Zhenan
Z
Mao
Yuanqing
Y
Liu
Ming
M
Tang
Tingting
T
Qiu
Shijing
S
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D001862:Bone Resorption / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D014025:Titanium / Q000494:pharmacology*
D016207:Cytokines; D018836:Inflammation Mediators; D050778:NFATC Transcription Factors; D009842:Oligopeptides; C121611:VIVIT peptide; D014025:Titanium