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Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background:Kir2.1 channels are responsible for membrane hyperpolarization of many cell types. While these Kir2.1 channels are known to be necessary for proper bone development and play a critical role in osteogenesis, the underlying mechanisms remain poorly understood. Here, we examined the effect of Kir2.1-mediated membrane hyperpolarization on the osteogenic differentiation of human dental follicle stem cells (hDFCs), a type of mesenchymal stem cell (MSC), and explored the underlying mechanisms.Methods:Levels of Kir2.1 and osteogenic marker expression were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Alkaline phosphatase (ALP) and Alizarin red staining were employed to evaluate ALP enzymatic activity and mineralized nodule formation, respectively. Intracellular Ca2+ levels were measured using fluorescent Ca2+ indicators with Ca2+ imaging.Results:Reversal of membrane hyperpolarization via modulation of extracellular K+ concentration ([K+]e) was shown to suppress osteogenic differentiation of hDFCs, whereas the induction of membrane hyperpolarization through the opening of ATP-sensitive K+ channels had the opposite effect, enhancing hDFC osteogenesis. Kir2.1 channel expression was upregulated during the osteogenic differentiation of hDFCs. Inhibition of Kir2.1 using short hairpin RNA (shRNA) or a pharmacological inhibitor suppressed osteogenic differentiation. Hyperpolarizing the membrane by decreasing [K+]e led to the elevation of intracellular Ca2+ levels, whereas this effect was eliminated by the removal of extracellular Ca2+, Kir2.1 inhibition, or treatment with La3+, a store-operated Ca2+ channel (SOC) blocker.Conclusions:Our findings indicate that membrane hyperpolarization promotes osteogenic differentiation of hDFCs by increasing intracellular Ca2+ levels and that the Kir2.1 and SOC channels play important roles in this process.<\/jats:p>","DOI":"10.31083\/fbl53140","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:35:31Z","timestamp":1788438931000},"source":"Crossref","is-referenced-by-count":0,"title":["Membrane Potential Hyperpolarization Controls the Osteogenic Differentiation of Human Dental Follicle Stem Cells by Increasing Intracellular Ca2+ Levels"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0291-0421","authenticated-orcid":true,"given":"Yidan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatology Hospital, Southwest Medical University, 646000 Luzhou, Sichuan, China"},{"name":"Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatology Hospital, Southwest Medical University, 646000 Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7898-7878","authenticated-orcid":true,"given":"Weijia","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatology Hospital, Southwest Medical University, 646000 Luzhou, Sichuan, China"},{"name":"Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatology Hospital, Southwest Medical University, 646000 Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1418-7561","authenticated-orcid":true,"given":"Dan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatology Hospital, Southwest Medical University, 646000 Luzhou, Sichuan, China"},{"name":"Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatology Hospital, Southwest Medical University, 646000 Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0890-0496","authenticated-orcid":true,"given":"Yuyang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatology Hospital, Southwest Medical University, 646000 Luzhou, Sichuan, China"},{"name":"Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatology Hospital, Southwest Medical University, 646000 Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatology Hospital, Southwest Medical University, 646000 Luzhou, Sichuan, China"},{"name":"Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatology Hospital, Southwest Medical University, 646000 Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2243-9124","authenticated-orcid":true,"given":"Dongchuan","family":"Zuo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, 646000 Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1545-0947","authenticated-orcid":true,"given":"Jin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatology Hospital, Southwest Medical University, 646000 Luzhou, Sichuan, China"},{"name":"Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatology Hospital, Southwest Medical University, 646000 Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Morsczeck C, Reichert TE. 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