PMID- 35693933
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 10
DP  - 2022
TI  - Connexin 43 Hemichannels Regulate Osteoblast to Osteocyte Differentiation.
PG  - 892229
LID - 10.3389/fcell.2022.892229 [doi]
LID - 892229
AB  - Connexin 43 (Cx43) is the predominant connexin subtype expressed in osteocytes. 
      Osteocytes, accounting for 90%-95% of total bone cells, function as orchestrators 
      coordinating balanced activity between bone-resorbing osteoclasts and 
      bone-forming osteoblasts. In this study, two newly developed osteocytic cell 
      lines, OCY454 and IDG-SW3, were used to determine the role of Cx43 gap junctions 
      and hemichannels (HCs) in the regulation of osteoblast to osteocyte 
      differentiation. We found that the Cx43 level was substantially increased during 
      the differentiation of IDG-SW3 cells and is also much higher than that of OCY454 
      cells. We knocked down Cx43 expression using the lentiviral CRISPR/Cas9 approach 
      and inhibition of Cx43 HCs using Cx43 (E2) antibody in IDG-SW3 cells. Cx43 
      knockdown (KD) or Cx43 HC inhibition decreased gene expression for osteoblast and 
      osteocyte markers, including alkaline phosphatase, type I collagen, dentin matrix 
      protein 1, sclerostin, and fibroblast growth factor 23, whereas increasing the 
      osteoclastogenesis indicator and the receptor activator of nuclear factor kappa-B 
      ligand (RANKL)/osteoprotegerin (OPG) ratio at early and late differentiation 
      stages. Moreover, mineralization was remarkably attenuated in differentiated 
      Cx43-deficient IDG-SW3 cells compared to ROSA26 control. The conditioned medium 
      collected from fully differentiated IDG-SW3 cells with Cx43 KD promoted 
      osteoclastogenesis of RAW264.7 osteoclast precursors. Our results demonstrated 
      that Cx43 HCs play critical roles in osteoblast to osteocyte differentiation 
      process and regulate osteoclast differentiation via secreted factors.
CI  - Copyright (c) 2022 Hua, Gu and Jiang.
FAU - Hua, Rui
AU  - Hua R
AD  - Department of Biochemistry and Structural Biology, University of Texas Health 
      Science Center, San Antonio, TX, United States.
FAU - Gu, Sumin
AU  - Gu S
AD  - Department of Biochemistry and Structural Biology, University of Texas Health 
      Science Center, San Antonio, TX, United States.
FAU - Jiang, Jean X
AU  - Jiang JX
AD  - Department of Biochemistry and Structural Biology, University of Texas Health 
      Science Center, San Antonio, TX, United States.
LA  - eng
PT  - Journal Article
DEP - 20220527
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC9184820
OTO - NOTNLM
OT  - CRISPR/Cas9
OT  - Cx43
OT  - IDG-SW3 cells
OT  - mineralization
OT  - osteoblast differentiation
OT  - osteoclastogenesis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/06/14 06:00
MHDA- 2022/06/14 06:01
PMCR- 2022/01/01
CRDT- 2022/06/13 03:23
PHST- 2022/03/08 00:00 [received]
PHST- 2022/04/18 00:00 [accepted]
PHST- 2022/06/13 03:23 [entrez]
PHST- 2022/06/14 06:00 [pubmed]
PHST- 2022/06/14 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 892229 [pii]
AID - 10.3389/fcell.2022.892229 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2022 May 27;10:892229. doi: 10.3389/fcell.2022.892229. 
      eCollection 2022.