PMID- 31972221
OWN - NLM
STAT- MEDLINE
DCOM- 20201109
LR  - 20201109
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 388
IP  - 2
DP  - 2020 Mar 15
TI  - PP121 suppresses RANKL-Induced osteoclast formation in vitro and LPS-Induced bone 
      resorption in vivo.
PG  - 111857
LID - S0014-4827(20)30051-3 [pii]
LID - 10.1016/j.yexcr.2020.111857 [doi]
AB  - Bone resorption, caused by osteoclasts (OCs), is important to bone homeostasis. 
      The abnormalities of bone resorption may induce a series of diseases, including 
      osteoarthritis, osteoporosis and aseptic peri-implant loosening. The latest 
      research developed,a novel tyrosine and phosphoinositide kinase dual inhibitor, 
      named PP121, inhibited Src in anaplastic thyroid carcinoma cell. However, the 
      therapeutic function of PP121 on abnormal bone resorption is still uncertain. In 
      the present study, we showed that PP121 could potently suppress osteoclast 
      differentiation, osteoclast-specific gene expression and bone resorption via 
      suppressing Src/MAPK (ERK and p38)/Akt-mediated NFATc1 induction in vitro. \It 
      was found that PP121 could suppress the formation of osteoclasts from bone marrow 
      macrophages (BMMs) without causing cytotoxicity, inhibit bone resorption and 
      downregulate the mRNA level of osteoclast-specific markers, including calcitonin 
      receptor (CTR), tartrate resistant acid phosphatase (TRAP), cathepsin K (CTSK), 
      matrix metalloproteinase 3 (MMP3), Cellular oncogene fos (C-Fos) and nuclear 
      factor of activated T-cells cytoplasmic 1 (NFATc1). Consistent with in vitro 
      observation, we found that PP121 greatly ameliorated LPS-induced bone resorption. 
      Our results provide promising evidence of the therapeutic potential of PP121 for 
      osteolytic diseases related to excessive osteoclast-mediated bone resorption.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Zhou, Zhihang
AU  - Zhou Z
AD  - Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of 
      Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key 
      Laboratory of Stomatology & Shanghai Research Institute of Stomatology, People's 
      Republic of China.
FAU - Chen, Xinwei
AU  - Chen X
AD  - Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of 
      Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key 
      Laboratory of Stomatology & Shanghai Research Institute of Stomatology, People's 
      Republic of China.
FAU - Chen, Xuzhuo
AU  - Chen X
AD  - Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of 
      Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key 
      Laboratory of Stomatology & Shanghai Research Institute of Stomatology, People's 
      Republic of China.
FAU - Qin, An
AU  - Qin A
AD  - Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, 
      Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, People's Republic of China.
FAU - Mao, Yi
AU  - Mao Y
AD  - Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of 
      Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key 
      Laboratory of Stomatology & Shanghai Research Institute of Stomatology, People's 
      Republic of China.
FAU - Pang, Yichuan
AU  - Pang Y
AD  - Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of 
      Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key 
      Laboratory of Stomatology & Shanghai Research Institute of Stomatology, People's 
      Republic of China.
FAU - Yu, Shiqi
AU  - Yu S
AD  - Shanghai Ninth People's Hospital, School of Biomedical Engineering, Shanghai Jiao 
      Tong University, Shanghai, People's Republic of China.
FAU - Zhang, Shanyong
AU  - Zhang S
AD  - Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of 
      Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key 
      Laboratory of Stomatology & Shanghai Research Institute of Stomatology, People's 
      Republic of China. Electronic address: zhangshanyong@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200120
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Lipopolysaccharides)
RN  - 0 (PP121 compound)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - 0 (RANK Ligand)
RN  - 0 (Tnfsf11 protein, mouse)
SB  - IM
MH  - Animals
MH  - Bone Resorption/chemically induced/*drug therapy/metabolism/pathology
MH  - *Cell Differentiation
MH  - Lipopolysaccharides/*toxicity
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Osteoclasts/*drug effects/metabolism
MH  - *Osteogenesis
MH  - Pyrazoles/*pharmacology
MH  - Pyrimidines/*pharmacology
MH  - RANK Ligand/genetics/*metabolism
OTO - NOTNLM
OT  - Bone resorption
OT  - Osteoclasts
OT  - PP121
OT  - RANKL
OT  - Src
COIS- Declaration of competing interest The authors declare no conflict of interest.
EDAT- 2020/01/24 06:00
MHDA- 2020/11/11 06:00
CRDT- 2020/01/24 06:00
PHST- 2019/10/20 00:00 [received]
PHST- 2020/01/08 00:00 [revised]
PHST- 2020/01/19 00:00 [accepted]
PHST- 2020/01/24 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2020/01/24 06:00 [entrez]
AID - S0014-4827(20)30051-3 [pii]
AID - 10.1016/j.yexcr.2020.111857 [doi]
PST - ppublish
SO  - Exp Cell Res. 2020 Mar 15;388(2):111857. doi: 10.1016/j.yexcr.2020.111857. Epub 
      2020 Jan 20.