{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:20:13Z","timestamp":1785406813249,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470945"],"award-info":[{"award-number":["82470945"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82470945"],"award-info":[{"award-number":["82470945"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Orthodontic tooth movement (OTM) is driven by force-induced alveolar bone remodeling, yet the molecular mechanisms by which periodontal ligament stem cells (PDLSCs) sense and transduce mechanical signals remain incompletely understood. Here, we identify the epigenetic regulator HELLS as a compressive force-responsive gene and investigate its role as a mechanosensitive mediator in human PDLSCs (hPDLSCs). Compressive force downregulated HELLS expression both in vitro and in a mouse OTM model. Functionally, siRNA-mediated HELLS knockdown impaired osteogenic differentiation, as evidenced by reduced Alizarin Red S staining and alkaline phosphatase activity, and induced global transcriptomic changes indicative of altered mechanotransduction pathways. Moreover, HELLS knockdown increased YAP and RANKL expression and potentiated osteoclast differentiation of co-cultured RAW264.7 cells. Finally, we identified E2F1 as a candidate transcription factor mediating the force-induced downregulation of HELLS. Collectively, these findings establish HELLS as a potential mechano-epigenetic regulator in hPDLSCs, and suggest that its force-induced downregulation may contribute to alveolar bone remodeling during OTM by simultaneously attenuating osteogenesis and enhancing pro-osteoclastogenic signaling via transcriptional reprogramming.<\/jats:p>","DOI":"10.3390\/ijms27104540","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:55:28Z","timestamp":1779180928000},"page":"4540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HELLS Reduction Contributes to Compressive Force-Induced Functional Changes in PDLSCs"],"prefix":"10.3390","volume":"27","author":[{"given":"Manqi","family":"Wang","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China"},{"name":"National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China"},{"name":"Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China"},{"name":"National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China"},{"name":"Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China"},{"name":"National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China"},{"name":"Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4584-1092","authenticated-orcid":false,"given":"Bing","family":"Han","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China"},{"name":"National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China"},{"name":"Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China"},{"name":"National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China"},{"name":"Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/prd.12194","article-title":"Effect of orthodontic treatment on the periodontal tissues","volume":"74","author":"Antoun","year":"2017","journal-title":"Periodontol. 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