Connexin 43 and ERK regulate tension-induced signal transduction in human periodontal ligament fibroblasts

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Shengnan LiDing Zhang

Abstract

Periodontal ligament (PDL) fibroblasts play an important role in preserving periodontal homeostasis and transmitting mechanical signals to alveolar bone. Connexin 43 (Cx43), a gap junction protein, is essential for bone homeostasis and regulates bone remodeling. However, the function of Cx43 in human PDL fibroblast-regulated bone remodeling has not yet been elucidated. In this study, human PDL fibroblasts were exposed to cyclic mechanical tension with a maximum 5% elongation for different durations. We then examined the expression of signaling molecules related to osteogenesis and osteoclastogenesis at both the mRNA and protein levels as well as the activity of extracellular signal-regulated kinase (ERK) in human PDL fibroblasts after loading. We found that mechanical tension increased Cx43, which further upregulated osteogenic (e.g., RUNX2, Osterix, and OPG) and down-regulated osteoclastogenic (e.g., RANKL) signaling molecules. Suppressing Cx43 gene (Gja1) by siRNA inhibited the increase in osteogenesis-related molecules but enhanced RANKL expression. Similar to Cx43, activated ERK1/2 was also enhanced by mechanical tension and suppressed by Cx43 siRNA. Inhibition of ERK1/2 signaling using PD98059 reduced the tension-regulated...Continue Reading

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Citations

Jun 21, 2015·Cellular and Molecular Life Sciences : CMLS·Lilian I Plotkin, Joseph P Stains
Jul 15, 2016·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·K Q LiD S Zhang
Feb 28, 2017·Scientific Reports·Cheng-Hu HuYan Jin
Jun 27, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ei Ei Hsu HlaingHiroshi Kamioka
Jun 26, 2018·Progress in Orthodontics·Amarjot SinghHarpal Jakhu
Apr 19, 2017·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Atum M BuoJoseph P Stains
Jun 28, 2016·Experimental and Therapeutic Medicine·Ying-Yan ZhouYi-Ting He
May 2, 2019·BMC Molecular and Cell Biology·Hiroyuki KanzakiYoshiki Nakamura
Nov 17, 2020·Advanced Healthcare Materials·Sanja AveicHorst Fischer
May 1, 2021·Journal of Clinical Medicine·Hyeran Helen JeonAndrew Tsai
Sep 14, 2021·Frontiers in Bioengineering and Biotechnology·Changyun SunUwe Baumert

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