{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:08:09Z","timestamp":1790078889231,"version":"4.0.1"},"reference-count":31,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["22K10258"],"award-info":[{"award-number":["22K10258"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Hypertension is associated with abnormal bone metabolism and enhanced bone resorption, and altered sympathetic\/adrenergic signaling has been proposed as one contributing mechanism. Orthodontically induced inflammatory root resorption (OIRR) involves periodontal ligament inflammation, odontoclast induction, and the resorption of cementum and dentin. This study investigated whether the SHR phenotype is associated with greater OIRR and whether the pharmacological blockade of \u03b22-adrenergic receptor (\u03b22-AR) signaling with butoxamine (BTX) modulates these changes. Methods: A 50 gf Ni-Ti closed-coil spring was placed between the maxillary incisors and left first molar in SHRs and Wistar\u2013Kyoto (WKY) rats for 21 days, beginning 7 days after BTX administration. Animals were assigned to WKY(control), WKY(BTX), SHR(control), and SHR(BTX) groups. The tooth-movement distance, root length, and root volume were assessed via micro-computed tomography. The odontoclast number and surface, TNF-\u03b1, IL-1\u03b2, and \u03b22-AR immunoreactivity, cementocyte density, empty lacunae ratio, and TUNEL-positive cells within cementocyte lacunae were evaluated histologically. Results: Compared with WKY(control), SHR(control) showed greater tooth movement, a reduced root length and volume, an increased odontoclast number and surface, greater TNF-\u03b1- and IL-1\u03b2-positive areas, a lower cementocyte density, a higher empty lacunae ratio, and more TUNEL-positive cells within cementocyte lacunae. These root resorption- and inflammation-related changes were significantly attenuated in SHR(BTX) compared with SHR(control). Conclusions: The SHR phenotype was associated with increased OIRR, and the attenuation observed following \u03b22-AR blockade supports a potential contribution of adrenergic signaling to this response.<\/jats:p>","DOI":"10.3390\/jcm15187271","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:09:35Z","timestamp":1790075375000},"page":"7271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Orthodontic Root Resorption in Spontaneously Hypertensive Rats: Modulation by \u03b22-Adrenergic Receptor Blockade"],"prefix":"10.3390","volume":"15","author":[{"given":"Tomoma","family":"Yoshida","sequence":"first","affiliation":[{"name":"Department of Orthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5555-7709","authenticated-orcid":false,"given":"Takuma","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mifumi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Tabuchi","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Miyazawa","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1161\/HYPERTENSIONAHA.123.21648","article-title":"Advanced Progress of the Relationship Between Antihypertensive Drugs and Bone Metabolism","volume":"80","author":"Zhang","year":"2023","journal-title":"Hypertension"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Huang, Y., and Ye, J. (2024). Association between hypertension and osteoporosis: A population-based cross-sectional study. BMC Musculoskelet. Disord., 25.","DOI":"10.1186\/s12891-024-07553-4"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1007\/s00198-017-4050-z","article-title":"Meta-analysis of hypertension and osteoporotic fracture risk in women and men","volume":"28","author":"Li","year":"2017","journal-title":"Osteoporos. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"68916","DOI":"10.18632\/oncotarget.20325","article-title":"Association between essential hypertension and bone mineral density: A systematic review and meta-analysis","volume":"8","author":"Ye","year":"2017","journal-title":"Oncotarget"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0092-8674(02)01049-8","article-title":"Leptin regulates bone formation via the sympathetic nervous system","volume":"111","author":"Takeda","year":"2002","journal-title":"Cell"},{"key":"ref_6","first-page":"94","article-title":"Adrenergic control of bone remodeling and its implications for the treatment of osteoporosis","volume":"8","author":"Bonnet","year":"2008","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ejphar.2012.12.016","article-title":"Dose effects of butoxamine, a selective beta2-adrenoceptor antagonist, on bone metabolism in spontaneously hypertensive rat","volume":"701","author":"Arai","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1177\/0022034514536730","article-title":"Selective \u03b22-adrenergic Antagonist Butoxamine Reduces Orthodontic Tooth Movement","volume":"93","author":"Sato","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/ejo\/cjab072","article-title":"Orthodontic tooth movement-activated sensory neurons contribute to enhancing osteoclast activity and tooth movement through sympathetic nervous signalling","volume":"44","author":"Kondo","year":"2022","journal-title":"Eur. J. Orthod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1902\/jop.2010.090705","article-title":"Hypertension may affect tooth-supporting alveolar bone quality: A study in rats","volume":"81","author":"Bastos","year":"2010","journal-title":"J. Periodontol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119593","DOI":"10.1016\/j.lfs.2021.119593","article-title":"Effects of a beta2-adrenergic receptor blocker on experimental periodontitis in spontaneously hypertensive rats","volume":"277","author":"Takeguchi","year":"2021","journal-title":"Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/ejo\/15.4.249","article-title":"The initial phase of orthodontic root resorption incident to local compression of the periodontal ligament","volume":"15","author":"Brudvik","year":"1993","journal-title":"Eur. J. Orthod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"469.e1","DOI":"10.1016\/j.ajodo.2005.10.007","article-title":"Cellular, molecular, and tissue-level reactions to orthodontic force","volume":"129","author":"Krishnan","year":"2006","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20190108","DOI":"10.1098\/rsif.2019.0108","article-title":"In vivo effects of different orthodontic loading on root resorption and correlation with mechanobiological stimulus in periodontal ligament","volume":"16","author":"Zhong","year":"2019","journal-title":"J. R Soc. Interface"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1093\/ejo\/cjad011","article-title":"Under pressure-mechanisms and risk factors for orthodontically induced inflammatory root resorption: A systematic review","volume":"45","author":"Dawood","year":"2023","journal-title":"Eur. J. Orthod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/ejo\/cji015","article-title":"Orthodontically induced root and alveolar bone resorption: Inhibitory effect of systemic doxycycline administration in rats","volume":"27","author":"Mavragani","year":"2005","journal-title":"Eur. J. Orthod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1111\/odi.13280","article-title":"Suppression of tooth movement-induced sclerostin expression using beta-adrenergic receptor blockers","volume":"26","author":"Uchibori","year":"2020","journal-title":"Oral Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.bone.2007.04.194","article-title":"Local delivery of osteoprotegerin inhibits mechanically mediated bone modeling in orthodontic tooth movement","volume":"41","author":"Dunn","year":"2007","journal-title":"Bone"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.17576\/jsm-2022-5110-21","article-title":"Orthodontic induced inflammatory root resorption: The process involved and its management","volume":"51","author":"Hong","year":"2022","journal-title":"Sains Malays."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cosarca, A.S., Campana, M.D., Aliberti, A., Giordano, F., Ormenisan, A., Riccitiello, F., and Gasparro, R. (2026). Periodontal outcomes of surgically\u2013orthodontically treated impacted maxillary canines: Influence of surgical technique and impaction site\u2014A systematic review. Appl. Sci., 16.","DOI":"10.3390\/app16104871"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1254\/fpj.145.140","article-title":"Regulation of bone metabolism by sympathetic nervous system","volume":"145","author":"Togari","year":"2015","journal-title":"Nihon Yakurigaku Zasshi"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1902\/jop.2007.060321","article-title":"Actinobacillus actinomycetemcomitans lipopolysaccharide-mediated experimental bone loss model for aggressive periodontitis","volume":"78","author":"Rogers","year":"2007","journal-title":"J. Periodontol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.jphs.2021.08.003","article-title":"Guanabenz inhibits alveolar bone resorption in a rat model of periodontitis","volume":"147","author":"Muramatsu","year":"2021","journal-title":"J. Pharmacol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"416","DOI":"10.2319\/071116-541.1","article-title":"Cementocyte cell death occurs in rat cellular cementum during orthodontic tooth movement","volume":"87","author":"Matsuzawa","year":"2017","journal-title":"Angle Orthod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s11914-014-0194-3","article-title":"Apoptotic osteocytes and the control of targeted bone resorption","volume":"12","author":"Plotkin","year":"2014","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s002230010021","article-title":"Cell death of osteocytes occurs in rat alveolar bone during experimental tooth movement","volume":"70","author":"Hamaya","year":"2002","journal-title":"Calcif. Tissue Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.2319\/110713-813.1","article-title":"Osteocyte death during orthodontic tooth movement in mice","volume":"84","author":"Moin","year":"2014","journal-title":"Angle Orthod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101873","DOI":"10.1016\/j.bonr.2025.101873","article-title":"Partial cementocyte ablation does not reduce cellular cementum apposition in a mouse model of molar super-eruption","volume":"26","author":"Mohamed","year":"2025","journal-title":"Bone Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"116139","DOI":"10.1016\/j.bone.2021.116139","article-title":"Orthodontic tooth movement alters cementocyte ultrastructure and cellular cementum proteome signature","volume":"153","author":"Chavez","year":"2021","journal-title":"Bone"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41413-026-00538-0","article-title":"SphK1\/mitophagy axis in cementocytes drives orthodontic root resorption via mitochondrial transfer to osteoclasts","volume":"14","author":"Wang","year":"2026","journal-title":"Bone Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1172\/JCI114487","article-title":"Defective venous beta-adrenergic response in borderline hypertensive subjects is corrected by a low sodium diet","volume":"85","author":"Feldman","year":"1990","journal-title":"J. Clin. Investig."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7271\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:28:49Z","timestamp":1790076529000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":31,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15187271"],"URL":"https:\/\/doi.org\/10.3390\/jcm15187271","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]}}}