Enhancement of osteoblast differentiation that is inhibited by titanium particles through inactivation of NFATc1 by VIVIT peptide.
Bone formation, which is inhibited by particulate wear debris, is a pathological factor that contributes to periprosthetic osteolysis. Although the nuclear factor of activated T cells c1 (NFATc1) is known to be involved in osteoblast differentiation, and its effect on osteoblasts in response to wear particles remains unclear. In this study, we investigated the role of NFATc1 in the regulation of osteoblastic differentiation of rat calvaria (RC) cells (a cell-culture model comprising many osteoprogenitors) that were challenged with titanium (Ti) particles. The results showed that the Ti particles inhibited osteoblastic differentiation and mineralization of RC cells. NFATc1 plays a critical role in the Ti-particle inhibition process of the osteoblastic differentiation in RC cells. Inactivation of NFATc1 by the 11R-VIVIT peptide potently enhanced osteoblast differentiation and mineralization inhibition by the Ti particles. The 11R-VIVIT peptide does not have a toxic effect on the RC cells. On the basis of these data, we conclude that inactivation of NFATc1 by the 11R-VIVIT peptide may provide a promising therapeutic target for the treatment of periprosthetic osteolysis by increasing bone formation.
Maoqiang
Li
L
Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, China.
Zhenan
Zhu
Z
Fengxiang
Liu
L
Gang
Wang
W
Yuanqing
Mao
M
Ming
Liu
L
Xin
Zhao
Z
Tingting
Tang
T
D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D008297:Male; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors*; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000166:cytology; D014025:Titanium / Q000494:pharmacology*
D050778:NFATC Transcription Factors; D009842:Oligopeptides; C121611:VIVIT peptide; D014025:Titanium