2022
DOI: 10.1186/s13018-022-03230-1
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The role of the Smad2/3/4 signaling pathway in osteogenic differentiation regulation by ClC-3 chloride channels in MC3T3-E1 cells

Abstract: Background ClC-3 chloride channels promote osteogenic differentiation. Transforming growth factor-β1 (TGF-β1) and its receptors are closely related to ClC-3 chloride channels, and canonical TGF-β1 signaling is largely mediated by Smad proteins. The current study aimed to explore the role of the Smad2/3/4 signaling pathway in the mechanism by which ClC-3 chloride channels regulate osteogenic differentiation in osteoblasts. Methods First, real-time P… Show more

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Cited by 2 publications
(3 citation statements)
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“…According to previous studies, it is proposed that the BMPR1A protein activates SMAD proteins by binding to ligands in the TGF-β signaling pathway [ 63 , 64 , 65 ]. The Smad2/3/4 signaling pathway in osteoblasts regulates osteogenic differentiation of MC3T3-E1 cells through modulation of ClC-3 chloride channels [ 66 ]. The TGF-β family is believed to have arisen during multicellular (metazoan) evolution and is highly conserved [ 67 , 68 , 69 , 70 ].…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…According to previous studies, it is proposed that the BMPR1A protein activates SMAD proteins by binding to ligands in the TGF-β signaling pathway [ 63 , 64 , 65 ]. The Smad2/3/4 signaling pathway in osteoblasts regulates osteogenic differentiation of MC3T3-E1 cells through modulation of ClC-3 chloride channels [ 66 ]. The TGF-β family is believed to have arisen during multicellular (metazoan) evolution and is highly conserved [ 67 , 68 , 69 , 70 ].…”
Section: Discussionmentioning
confidence: 99%
“…The function of ClC-3 in bone differentiation may be through the Runx2 gene pathway, which mediates bone formation and remodeling [ 75 ]. Xiaolin Lu et al discovered that changes in ClC-3 chloride channels affect Smad2/3 proteins, demonstrating that the Smad2/3/4 signaling pathway inhibits the regulation of osteogenic differentiation in MC3T3-E1 cells [ 66 ]. ClC-3 is expressed in intracellular organelles of osteoclasts and promotes osteoclast bone resorption in vitro via organelle acidification [ 76 ].…”
Section: Discussionmentioning
confidence: 99%
“…Protein levels of this channel substantially increase in osteoporosis patients, demonstrating an interesting correlation and making it a highly interesting drug target candidate [ 100 ]. ClC-3 chloride channels are positive regulators of osteogenic differentiation in osteoblasts [ 101 ].…”
Section: Ion Channels Involved In Progenitor Cell Differentiationmentioning
confidence: 99%