PMID- 36370067
OWN - NLM
STAT- MEDLINE
DCOM- 20230109
LR  - 20230215
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 38
IP  - 1
DP  - 2023 Jan
TI  - Osteoblastic STAT3 Is Crucial for Orthodontic Force Driving Alveolar Bone 
      Remodeling and Tooth Movement.
PG  - 214-227
LID - 10.1002/jbmr.4744 [doi]
AB  - Mechanical force is essential to shape the internal architecture and external 
      form of the skeleton by regulating the bone remodeling process. However, the 
      underlying mechanism of how the bone responds to mechanical force remains 
      elusive. Here, we generated both orthodontic tooth movement (OTM) model in vivo 
      and a cyclic stretch-loading model in vitro to investigate biomechanical 
      regulation of the alveolar bone. In this study, signal transducer and activator 
      of transcription 3 (STAT3) was screened as one of the mechanosensitive proteins 
      by protein array analysis of cyclic stretch-loaded bone mesenchymal stem cells 
      (BMSCs) and was also proven to be activated in osteoblasts in response to the 
      mechanical force during OTM. With an inducible osteoblast linage-specific Stat3 
      knockout model, we found that Stat3 deletion decelerated the OTM rate and reduced 
      orthodontic force-induced bone remodeling, as indicated by both decreased bone 
      resorption and formation. Both genetic deletion and pharmacological inhibition of 
      STAT3 in BMSCs directly inhibited mechanical force-induced osteoblast 
      differentiation and impaired osteoclast formation via osteoblast-osteoclast 
      cross-talk under mechanical force loading. According to RNA-seq analysis of 
      Stat3-deleted BMSCs under mechanical force, matrix metalloproteinase 3 (Mmp3) was 
      screened and predicted to be a downstream target of STAT3. The luciferase and 
      ChIP assays identified that Stat3 could bind to the Mmp3 promotor and upregulate 
      its transcription activity. Furthermore, STAT3-inhibitor decelerated tooth 
      movement through inhibition of the bone resorption activity, as well as MMP3 
      expression. In summary, our study identified the mechanosensitive characteristics 
      of STAT3 in osteoblasts and highlighted its critical role in force-induced bone 
      remodeling during orthodontic tooth movement via osteoblast-osteoclast 
      cross-talk. (c) 2022 American Society for Bone and Mineral Research (ASBMR).
CI  - (c) 2022 American Society for Bone and Mineral Research (ASBMR).
FAU - Gong, Xinyi
AU  - Gong X
AD  - Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, College of Stomatology, Shanghai Jiao Tong University; National 
      Center for Stomatology; National Clinical Research Center for Oral Disease; 
      Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of 
      Stomatology, Shanghai, China.
FAU - Sun, Siyuan
AU  - Sun S
AD  - Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, College of Stomatology, Shanghai Jiao Tong University; National 
      Center for Stomatology; National Clinical Research Center for Oral Disease; 
      Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of 
      Stomatology, Shanghai, China.
FAU - Yang, Yiling
AU  - Yang Y
AD  - Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, College of Stomatology, Shanghai Jiao Tong University; National 
      Center for Stomatology; National Clinical Research Center for Oral Disease; 
      Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of 
      Stomatology, Shanghai, China.
FAU - Huang, Xiangru
AU  - Huang X
AD  - Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, College of Stomatology, Shanghai Jiao Tong University; National 
      Center for Stomatology; National Clinical Research Center for Oral Disease; 
      Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of 
      Stomatology, Shanghai, China.
FAU - Gao, Xin
AU  - Gao X
AD  - Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, College of Stomatology, Shanghai Jiao Tong University; National 
      Center for Stomatology; National Clinical Research Center for Oral Disease; 
      Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of 
      Stomatology, Shanghai, China.
FAU - Jin, Anting
AU  - Jin A
AD  - Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, College of Stomatology, Shanghai Jiao Tong University; National 
      Center for Stomatology; National Clinical Research Center for Oral Disease; 
      Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of 
      Stomatology, Shanghai, China.
FAU - Xu, Hongyuan
AU  - Xu H
AD  - Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, College of Stomatology, Shanghai Jiao Tong University; National 
      Center for Stomatology; National Clinical Research Center for Oral Disease; 
      Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of 
      Stomatology, Shanghai, China.
FAU - Wang, Xijun
AU  - Wang X
AD  - Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, College of Stomatology, Shanghai Jiao Tong University; National 
      Center for Stomatology; National Clinical Research Center for Oral Disease; 
      Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of 
      Stomatology, Shanghai, China.
FAU - Liu, Yuanqi
AU  - Liu Y
AD  - Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, College of Stomatology, Shanghai Jiao Tong University; National 
      Center for Stomatology; National Clinical Research Center for Oral Disease; 
      Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of 
      Stomatology, Shanghai, China.
FAU - Liu, Jingyi
AU  - Liu J
AD  - Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, College of Stomatology, Shanghai Jiao Tong University; National 
      Center for Stomatology; National Clinical Research Center for Oral Disease; 
      Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of 
      Stomatology, Shanghai, China.
FAU - Dai, Qinggang
AU  - Dai Q
AD  - The 2nd Dental Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Jiang, Lingyong
AU  - Jiang L
AUID- ORCID: 0000-0002-1624-4056
AD  - Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, College of Stomatology, Shanghai Jiao Tong University; National 
      Center for Stomatology; National Clinical Research Center for Oral Disease; 
      Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of 
      Stomatology, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221213
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
SB  - IM
MH  - Humans
MH  - *Matrix Metalloproteinase 3/metabolism
MH  - Tooth Movement Techniques
MH  - STAT3 Transcription Factor/metabolism
MH  - Periodontal Ligament/metabolism
MH  - Bone Remodeling/physiology
MH  - *Bone Resorption/metabolism
MH  - Osteoclasts/metabolism
OTO - NOTNLM
OT  - BONE REMODELING
OT  - MECHANICAL FORCE
OT  - ORTHODONTIC TOOTH MOVEMENT
OT  - OSTEOBLAST-OSTEOCLAST CROSS-TALK
OT  - SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3 (STAT3)
EDAT- 2022/11/13 06:00
MHDA- 2023/01/10 06:00
CRDT- 2022/11/12 08:02
PHST- 2022/10/08 00:00 [revised]
PHST- 2022/06/03 00:00 [received]
PHST- 2022/10/23 00:00 [accepted]
PHST- 2022/11/13 06:00 [pubmed]
PHST- 2023/01/10 06:00 [medline]
PHST- 2022/11/12 08:02 [entrez]
AID - 10.1002/jbmr.4744 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2023 Jan;38(1):214-227. doi: 10.1002/jbmr.4744. Epub 2022 Dec 
      13.