PMID- 36621148
OWN - NLM
STAT- MEDLINE
DCOM- 20230203
LR  - 20231213
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 644
DP  - 2023 Feb 12
TI  - CypD-mediated mitochondrial dysfunction contributes to titanium ion-induced 
      MC3T3-E1 cell injury.
PG  - 15-24
LID - S0006-291X(22)01767-3 [pii]
LID - 10.1016/j.bbrc.2022.12.088 [doi]
AB  - Titanium (Ti) ion can stimulate osteoblast apoptosis and therefore have a high 
      potential to play a negative role in the aseptic loosening of implants. 
      Mitochondrial abnormalities are closely related to osteoblast dysfunction. 
      However, the mitochondrial molecular mechanism of Ti ion induced osteoblastic 
      cell apoptosis is still unclear. This study investigated in vitro mitochondrial 
      oxidative stress (mtROS) mediated mitochondrial dysfunction involved in Ti 
      ion-induced apoptosis of murine MC3T3-E1 osteoblastic cells. In addition to 
      reducing mitochondrial membrane potential (MMP) and decreasing adenosine 
      triglyceride production, exposure to Ti ions increased mitochondrial oxidative 
      stress. Moreover, mitochondrial abnormalities significantly contributed to Ti ion 
      induction of osteoblastic cellular apoptosis. A mitochondria-specific 
      antioxidant, mitoquinone (MitoQ), alleviated Ti ion-induced mitochondrial 
      dysfunction and apoptosis in osteoblastic cells, indicating that Ti ion mainly 
      induces mitochondrial oxidative stress to produce a cytotoxic effect on 
      osteoblasts. Here we show that the primary regulator of mitochondrial 
      permeability transition pore (mPTP), cyclophilin D (CypD), is involved in 
      mitochondrial dysfunction and osteoblast cell apoptosis induced by Ti ion. 
      Overexpression of CypD exacerbates osteoblast apoptosis and impairs osteogenic 
      function. Moreover, detrimental effects of CypD were rescued by cyclosporin A 
      (CsA), an inhibitor of CypD, which shows its protective effect on mitochondrial 
      and osteogenic osteoblast functions. Based on new insights into the mitochondrial 
      mechanisms underlying Ti ion-induced apoptosis of osteoblastic cells, the 
      findings of this study lay the foundation for the clinical use of CypD inhibitors 
      to prevent or treat implant failure.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Mao, Yixin
AU  - Mao Y
AD  - Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical 
      University, Wenzhou, 325027, China; Institute of Stomatology, School and Hospital 
      of Stomatology, Wenzhou Medical University, Wenzhou, 325027, China; Laboratory 
      for Myology, Department of Human Movement Sciences, Faculty of Behavioural and 
      Movement Sciences, Vrije Universiteit Amsterdam (VUA), Amsterdam Movement 
      Sciences, Amsterdam, 1081, HZ, Netherlands.
FAU - Chen, Yang
AU  - Chen Y
AD  - Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical 
      University, Wenzhou, 325027, China; Institute of Stomatology, School and Hospital 
      of Stomatology, Wenzhou Medical University, Wenzhou, 325027, China.
FAU - Cai, Wenjin
AU  - Cai W
AD  - Stomatology Hospital, School of Stomatology, Zhejiang University School of 
      Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key 
      Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of 
      Zhejiang University, Hangzhou, 310000, China.
FAU - Jiang, Wanying
AU  - Jiang W
AD  - Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical 
      University, Wenzhou, 325027, China.
FAU - Sun, Xiaoyu
AU  - Sun X
AD  - Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical 
      University, Wenzhou, 325027, China.
FAU - Zeng, Jun
AU  - Zeng J
AD  - Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical 
      University, Wenzhou, 325027, China.
FAU - Wang, Hongning
AU  - Wang H
AD  - Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical 
      University, Wenzhou, 325027, China.
FAU - Wang, Xia
AU  - Wang X
AD  - Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical 
      University, Wenzhou, 325027, China.
FAU - Dong, Wenmei
AU  - Dong W
AD  - Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical 
      University, Wenzhou, 325027, China.
FAU - Ma, Jianfeng
AU  - Ma J
AD  - Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical 
      University, Wenzhou, 325027, China; Institute of Stomatology, School and Hospital 
      of Stomatology, Wenzhou Medical University, Wenzhou, 325027, China.
FAU - Jaspers, Richard T
AU  - Jaspers RT
AD  - Laboratory for Myology, Department of Human Movement Sciences, Faculty of 
      Behavioural and Movement Sciences, Vrije Universiteit Amsterdam (VUA), Amsterdam 
      Movement Sciences, Amsterdam, 1081, HZ, Netherlands.
FAU - Huang, Shengbin
AU  - Huang S
AD  - Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical 
      University, Wenzhou, 325027, China; Institute of Stomatology, School and Hospital 
      of Stomatology, Wenzhou Medical University, Wenzhou, 325027, China. Electronic 
      address: huangsb003@wmu.edu.cn.
FAU - Wu, Gang
AU  - Wu G
AD  - Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and 
      Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam 
      (VUA), Amsterdam Movement Science, Amsterdam, the Netherlands; Department of Oral 
      Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of 
      Amsterdam (UvA), Vrije Universiteit Amsterdam (VU), Amsterdam, the Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221231
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Peptidyl-Prolyl Isomerase F)
RN  - D1JT611TNE (Titanium)
RN  - EC 5.2.1.- (Cyclophilins)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 0 (Mitochondrial Membrane Transport Proteins)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Peptidyl-Prolyl Isomerase F/metabolism
MH  - *Titanium/pharmacology
MH  - *Oxidative Stress
MH  - Cyclophilins/metabolism
MH  - Cyclosporine/pharmacology
MH  - Mitochondria/metabolism
MH  - Mitochondrial Membrane Transport Proteins/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Cyclophilin D
OT  - Mitochondrial reactive oxygen species
OT  - Osteoblasts
OT  - Titanium ion
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/01/10 06:00
MHDA- 2023/02/04 06:00
CRDT- 2023/01/09 04:35
PHST- 2022/11/17 00:00 [received]
PHST- 2022/11/23 00:00 [revised]
PHST- 2022/12/30 00:00 [accepted]
PHST- 2023/01/10 06:00 [pubmed]
PHST- 2023/02/04 06:00 [medline]
PHST- 2023/01/09 04:35 [entrez]
AID - S0006-291X(22)01767-3 [pii]
AID - 10.1016/j.bbrc.2022.12.088 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2023 Feb 12;644:15-24. doi: 
      10.1016/j.bbrc.2022.12.088. Epub 2022 Dec 31.