PMID- 32286624
OWN - NLM
STAT- MEDLINE
DCOM- 20210107
LR  - 20210107
IS  - 1745-7270 (Electronic)
IS  - 1672-9145 (Linking)
VI  - 52
IP  - 5
DP  - 2020 May 26
TI  - Osteoporosis-decreased extracellular matrix stiffness impairs connexin 
      43-mediated gap junction intercellular communication in osteocytes.
PG  - 517-526
LID - 10.1093/abbs/gmaa025 [doi]
AB  - Osteocytes are the main sensitive and responsive cells for mechanical stimuli in 
      bone. The connexin family enables them to communicate with each other via forming 
      functional gap junctions. However, how osteoporosis-impaired extracellular 
      mechanical property modulates gap junction intercellular communication in 
      osteocytes remains elusive. In this study, we established an ovariectomy 
      (OVX)-induced osteoporosis mouse model in vivo and a polydimethylsiloxane 
      (PDMS)-based cell culture substrate model in vitro to explore the influence of 
      extracellular matrix (ECM) stiffness on cell-to-cell communication in osteocytes. 
      Firstly, we established an OVX-induced osteoporosis mouse model by characterizing 
      the changes in radiography, morphology and histochemistry of femurs. Our results 
      showed that osteoporosis decreased the bone matrix stiffness together with the 
      changes including the loss of osteocytes and the decrease of protein markers. 
      Meanwhile, the dendritic process interconnection and channel-forming protein, 
      Cx43, were reduced in osteoporosis mice. Next we mimicked ECM stiffness changes 
      in vitro by using PDMS substrates at ratios 1:5 for normal stiffness and 1:45 for 
      osteoporosis stiffness. Our results showed that the decreased ECM stiffness 
      reduced the number of dendritic processes in a single cell and gap junctions 
      between adjacent osteocytes. We further detected the decreased expression of 
      Cx43, in the substrate with decreased stiffness. Finally, we found that gap 
      junction-based intercellular communication was reduced in living osteocytes in 
      the substrate with decreased stiffness. This study demonstrates the correlation 
      between ECM mechanical property and cell-to-cell communication in osteocytes and 
      might pave the way for further exploration of osteoporosis in terms of 
      biomechanics.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the 
      Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological 
      Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, 
      please e-mail: journals.permissions@oup.com.
FAU - Zhang, Demao
AU  - Zhang D
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu 610064, China.
FAU - Li, Xin
AU  - Li X
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu 610064, China.
FAU - Pi, Caixia
AU  - Pi C
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu 610064, China.
FAU - Cai, Linyi
AU  - Cai L
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu 610064, China.
FAU - Liu, Yang
AU  - Liu Y
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu 610064, China.
FAU - Du, Wei
AU  - Du W
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu 610064, China.
FAU - Yang, Wenbin
AU  - Yang W
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu 610064, China.
AD  - National Clinical Research Center for Oral Diseases, West China Hospital of 
      Stomatology, Sichuan University, Chengdu 610064, China.
FAU - Xie, Jing
AU  - Xie J
AD  - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, 
      Sichuan University, Chengdu 610064, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Acta Biochim Biophys Sin (Shanghai)
JT  - Acta biochimica et biophysica Sinica
JID - 101206716
RN  - 0 (Connexin 43)
RN  - 0 (GJA1 protein, mouse)
RN  - 7LKK855W8I (Letrozole)
SB  - IM
MH  - Animals
MH  - *Cell Communication
MH  - Connexin 43/*metabolism
MH  - Disease Models, Animal
MH  - Extracellular Matrix/*metabolism/pathology
MH  - Gap Junctions/*metabolism/pathology
MH  - Letrozole
MH  - Mice
MH  - Osteocytes/*metabolism/pathology
MH  - Osteoporosis/*metabolism/pathology
OTO - NOTNLM
OT  - bone pathology
OT  - connexin43
OT  - gap junction
OT  - osteocytes
OT  - osteoporosis
EDAT- 2020/04/15 06:00
MHDA- 2021/01/08 06:00
CRDT- 2020/04/15 06:00
PHST- 2019/11/28 00:00 [received]
PHST- 2019/12/20 00:00 [revised]
PHST- 2020/02/24 00:00 [accepted]
PHST- 2020/04/15 06:00 [pubmed]
PHST- 2021/01/08 06:00 [medline]
PHST- 2020/04/15 06:00 [entrez]
AID - 5819536 [pii]
AID - 10.1093/abbs/gmaa025 [doi]
PST - ppublish
SO  - Acta Biochim Biophys Sin (Shanghai). 2020 May 26;52(5):517-526. doi: 
      10.1093/abbs/gmaa025.