{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T19:35:58Z","timestamp":1788464158452,"version":"build-2803163510"},"reference-count":29,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Periodontal ligament (PDL) cells are crucial for mechanosensation and mechanotransduction within the PDL, yet the role of primary cilia in orthodontic force transmission has not been examined. While bone morphogenetic protein (BMP) signaling significantly influences ciliary function, its effect on cellular responses to mechanical stress has not been investigated. This study aims to investigate whether primary cilia and BMP signaling are involved in the periodontal ligament\u2019s response to orthodontic tooth movement and the resultant mechanical strain. To visualize primary cilia, human PDL cells were cultured on glass-bottom dishes for five days, with a subset fixed daily, followed by immunostaining with anti-acetylated \u03b1-tubulin and Alexa Fluor 568 and imaging using a fluorescence microscope under 405 nm and 561 nm laser excitation. Human PDL cells were grown on Bioflex\u00ae culture plates and subsequently exposed to static tensile strains of 2.5%, 5%, 10%, 20%, on a FX-6000T\u2122 Tension System for 24 h. RT-qPCR was performed to evaluate changes in expression of primary cilia via Ift88 expression, mechanotransduction via Cox2 expression, and BMP signaling-related genes. Histological specimens from orthodontically loaded and control human premolars were investigated for primary cilia and BMP signaling using immunohistochemistry and confocal microscopy. Primary cilia were observed in PDL cells from day one, with their incidence and length increasing over time alongside cell density. BMP signaling components, including upregulated genes such as Bmp7 (10.99\u201314.97 fold), Alk2 (3.19\u20135.45 fold), and Bmpr2 (1.64\u20138.40 fold), consistently responded to strain, while Cox2 and Ift88 showed differential regulation depending on strain intensity. In vivo, orthodontic movement activated BMP signaling and increased primary cilium incidence in the PDL. These findings indicate the potential role of primary cilia and BMP signaling in the mechanosensitivity of PDL cells under orthodontic forces. Further studies are required to understand the complex mechanotransduction mechanisms and role of these components in cellular adaptation during orthodontic tooth movement.<\/jats:p>","DOI":"10.3390\/ijms252312648","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T06:25:19Z","timestamp":1732515919000},"page":"12648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigating the Role of Primary Cilia and Bone Morphogenetic Protein Signaling in Periodontal Ligament Response to Orthodontic Strain In Vivo and In Vitro: A Pilot Study"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5141-0550","authenticated-orcid":false,"given":"Emily R.","family":"Moore","sequence":"first","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0266-6095","authenticated-orcid":false,"given":"Anna","family":"Konermann","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University of Bonn, 53111 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1034\/j.1600-0757.2000.2240104.x","article-title":"Role of physical forces in regulating the form and function of the periodontal ligament","volume":"24","author":"McCulloch","year":"2000","journal-title":"Periodontol. 2000"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41368-021-00125-5","article-title":"Biomechanical and biological responses of periodontium in orthodontic tooth movement: Up-date in a new decade","volume":"13","author":"Li","year":"2021","journal-title":"Int. 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