{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T03:42:21Z","timestamp":1782186141607,"version":"3.54.5"},"reference-count":44,"publisher":"The Angle Orthodontist (EH Angle Education & Research Foundation)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objectives<\/jats:title>\n To examine whether lithium suppresses orthodontically induced root resorption (OIRR) via two mechanisms (prevention of hyalinization in periodontal tissue and suppression of odontoclasts) and to investigate the changes in the periodontal tissue and alveolar bone, focusing on the appearance of cell death, hyalinization, and odontoclasts.<\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n The maxillary first molars of 10-week-old male Wistar rats were moved mesially by a closed-coil spring for 14 days. Lithium chloride (LiCl; 0.64 mM\/kg) or saline (control) was administered intraperitoneally daily. Tooth movements were measured using micro\u2013computed tomography. Appearances of cell death, hyalinization, and odontoclasts were evaluated by histological analysis.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n OIRR observed on day 14 in the control group was suppressed strongly by LiCl administration. Apoptotic cells observed on day 1 in the compression area were gradually diminished on days 2 and 3 and transformed to hyalinization tissue in the control group. LiCl administration remarkably suppressed this cell death and subsequent hyalinization. Also, the appearance of odontoclasts in the compression area observed on day 7 was significantly suppressed by LiCl administration. Accordingly, these degenerative processes to OIRR were suppressed substantially by LiCl treatment.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Lithium reduces OIRR through the suppression of periodontal ligament cell death, hyalinization, and odontoclast formation.<\/jats:p>\n <\/jats:sec>","DOI":"10.2319\/072221-578.2","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T12:40:58Z","timestamp":1644237658000},"page":"547-554","source":"Crossref","is-referenced-by-count":5,"title":["Lithium reduces orthodontically induced root resorption by suppressing cell death, hyalinization, and odontoclast formation in rats"],"prefix":"10.2319","volume":"92","author":[{"given":"Yuika","family":"Ueda-Ichinose","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Hotokezaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Moriishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Hotokezaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keira","family":"Arizono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1164","reference":[{"issue":"(3)","key":"i1945-7103-92-4-547-b01","series-title":"Angle Orthod","first-page":"235","article-title":"Root resorption in bicuspid intrusion","volume":"52","author":"Harry","year":"1982","unstructured":"Harry\n MR,\n \n \n Harry\n MRS.\n \n \n Root resorption in bicuspid intrusion.\n\t\t\t\t\tAngle Orthod.\n\t\t\t\t\t1982;\n\t\t\t\t\t52(3):\n\t\t\t\t\t235\u2013\n\t\t\t\t\t258."},{"key":"i1945-7103-92-4-547-b02","series-title":"Nordisk Tandl\u00e4kare Tidskrift","first-page":"236","article-title":"Einige Beitr\u00e4ge zur Theorie der Zahnregulierung","volume":"5","author":"Sandstedt","year":"1904","unstructured":"Sandstedt\n C.\n \n \n Einige Beitr\u00e4ge zur Theorie der Zahnregulierung.\n\t\t\t\t\tNordisk Tandl\u00e4kare Tidskrift.\n\t\t\t\t\t1904;\n\t\t\t\t\t5:\n\t\t\t\t\t236\u2013\n\t\t\t\t\t256."},{"issue":"(2)","key":"i1945-7103-92-4-547-b03","series-title":"J Dent Res","first-page":"145","article-title":"Cellular and molecular pathways leading to external root resorption","volume":"96","author":"Iglesias-Linares","year":"2017","unstructured":"Iglesias-Linares\n A,\n \n \n Hartsfield\n JK.\n \n \n Cellular and molecular pathways leading to external root resorption.\n\t\t\t\t\tJ Dent Res.\n\t\t\t\t\t2017;\n\t\t\t\t\t96(2):\n\t\t\t\t\t145\u2013\n\t\t\t\t\t152."},{"issue":"(4)","key":"i1945-7103-92-4-547-b04","series-title":"Eur J Orthod","first-page":"249","article-title":"Root resorption beneath the main hyalinized zone","volume":"16","author":"Brudvik","year":"1994","unstructured":"Brudvik\n P,\n \n \n Rygh\n P.\n \n \n Root resorption beneath the main hyalinized zone.\n\t\t\t\t\tEur J Orthod.\n\t\t\t\t\t1994;\n\t\t\t\t\t16(4):\n\t\t\t\t\t249\u2013\n\t\t\t\t\t263."},{"issue":"(4)","key":"i1945-7103-92-4-547-b05","series-title":"Eur J Orthod","first-page":"249","article-title":"The initial phase of orthodontic root resorption incident to local compression of the periodontal ligament","volume":"15","author":"Brudvik","year":"1993","unstructured":"Brudvik\n P,\n \n \n Rygh\n P.\n \n \n The initial phase of orthodontic root resorption incident to local compression of the periodontal ligament.\n\t\t\t\t\tEur J Orthod.\n\t\t\t\t\t1993;\n\t\t\t\t\t15(4):\n\t\t\t\t\t249\u2013\n\t\t\t\t\t263."},{"issue":"(4)","key":"i1945-7103-92-4-547-b06","series-title":"Eur J Orthod","first-page":"346","article-title":"Effects of systemic medication on root resorption associated with orthodontic tooth movement: a systematic review of animal studies","volume":"41","author":"Makrygiannakis","year":"2019","unstructured":"Makrygiannakis\n MA,\n \n \n Kaklamanos\n EG,\n \n \n Athanasiou\n AE.\n \n \n Effects of systemic medication on root resorption associated with orthodontic tooth movement: a systematic review of animal studies.\n\t\t\t\t\tEur J Orthod.\n\t\t\t\t\t2019;\n\t\t\t\t\t41(4):\n\t\t\t\t\t346\u2013\n\t\t\t\t\t359."},{"issue":"(2)","key":"i1945-7103-92-4-547-b07","series-title":"Exp Ther Med","first-page":"468","article-title":"Lithium chloride attenuates root resorption during orthodontic tooth movement in rats","volume":"7","author":"Wang","year":"2014","unstructured":"Wang\n Y,\n \n \n Gao\n S,\n \n \n Jiang\n H,\n \n \n Lin\n P,\n \n \n Bao\n X.\n \n \n Lithium chloride attenuates root resorption during orthodontic tooth movement in rats.\n\t\t\t\t\tExp Ther Med.\n\t\t\t\t\t2014;\n\t\t\t\t\t7(2):\n\t\t\t\t\t468\u2013\n\t\t\t\t\t472."},{"issue":"(4)","key":"i1945-7103-92-4-547-b08","series-title":"Angle Orthod","first-page":"474","article-title":"Lithium chloride reduces orthodontically induced root resorption and affects tooth root movement in rats","volume":"88","author":"Ino-Kondo","year":"2018","unstructured":"Ino-Kondo\n A,\n \n \n Hotokezaka\n H,\n \n \n Kondo\n T,\n \n et al.\n \n Lithium chloride reduces orthodontically induced root resorption and affects tooth root movement in rats.\n\t\t\t\t\tAngle Orthod.\n\t\t\t\t\t2018;\n\t\t\t\t\t88(4):\n\t\t\t\t\t474\u2013\n\t\t\t\t\t482."},{"issue":"(9)","key":"i1945-7103-92-4-547-b09","series-title":"Trends Pharmacol Sci","first-page":"441","article-title":"Lithium and GSK-3: one inhibitor, two inhibitory actions, multiple outcomes","volume":"24","author":"Jope","year":"2003","unstructured":"Jope\n RS.\n \n \n Lithium and GSK-3: one inhibitor, two inhibitory actions, multiple outcomes.\n\t\t\t\t\tTrends Pharmacol Sci.\n\t\t\t\t\t2003;\n\t\t\t\t\t24(9):\n\t\t\t\t\t441\u2013\n\t\t\t\t\t443."},{"issue":"(6)","key":"i1945-7103-92-4-547-b10","series-title":"Nat Rev Drug Discov","first-page":"479","article-title":"GSK3 inhibitors: development and therapeutic potential","volume":"3","author":"Cohen","year":"2004","unstructured":"Cohen\n P,\n \n \n Goedert\n M.\n \n \n GSK3 inhibitors: development and therapeutic potential.\n\t\t\t\t\tNat Rev Drug Discov.\n\t\t\t\t\t2004;\n\t\t\t\t\t3(6):\n\t\t\t\t\t479\u2013\n\t\t\t\t\t487."},{"issue":"(10)","key":"i1945-7103-92-4-547-b11","series-title":"Nat Rev Mol Cell Biol","first-page":"769","article-title":"The renaissance of GSK3","volume":"2","author":"Cohen","year":"2001","unstructured":"Cohen\n P,\n \n \n Frame\n S.\n \n \n The renaissance of GSK3.\n\t\t\t\t\tNat Rev Mol Cell Biol.\n\t\t\t\t\t2001;\n\t\t\t\t\t2(10):\n\t\t\t\t\t769\u2013\n\t\t\t\t\t776."},{"issue":"(7)","key":"i1945-7103-92-4-547-b12","series-title":"Cell Death Dis","first-page":"1","article-title":"Lithium reduces apoptosis and autophagy after neonatal hypoxia-ischemia","volume":"1","author":"Li","year":"2010","unstructured":"Li\n Q,\n \n \n Li\n H,\n \n \n Roughton\n K,\n \n \n Wang\n X,\n \n \n Kroemer\n G,\n \n \n Blomgren\n K,\n \n \n Zhu\n C.\n \n \n Lithium reduces apoptosis and autophagy after neonatal hypoxia-ischemia.\n\t\t\t\t\tCell Death Dis.\n\t\t\t\t\t2010;\n\t\t\t\t\t1(7):\n\t\t\t\t\t1\u2013\n\t\t\t\t\t9."},{"issue":"(4)","key":"i1945-7103-92-4-547-b13","series-title":"Cell Death Dis","first-page":"1","article-title":"GSK-3\u03b2-dependent downregulation of \u03b3-taxilin and \u03b1NAC merge to regulate ER stress responses","volume":"6","author":"Hotokezaka","year":"2015","unstructured":"Hotokezaka\n Y,\n \n \n Katayama\n I,\n \n \n Van Leyen\n K,\n \n \n Nakamura\n T.\n \n \n GSK-3\u03b2-dependent downregulation of \u03b3-taxilin and \u03b1NAC merge to regulate ER stress responses.\n\t\t\t\t\tCell Death Dis.\n\t\t\t\t\t2015;\n\t\t\t\t\t6(4):\n\t\t\t\t\t1\u2013\n\t\t\t\t\t10."},{"issue":"(11)","key":"i1945-7103-92-4-547-b14","series-title":"Cell Death Differ","first-page":"1505","article-title":"\u03b1NAC depletion as an initiator of ER stress-induced apoptosis in hypoxia","volume":"16","author":"Hotokezaka","year":"2009","unstructured":"Hotokezaka\n Y,\n \n \n van Leyen\n K,\n \n \n Lo\n EH,\n \n et al.\n \n \u03b1NAC depletion as an initiator of ER stress-induced apoptosis in hypoxia.\n\t\t\t\t\tCell Death Differ.\n\t\t\t\t\t2009;\n\t\t\t\t\t16(11):\n\t\t\t\t\t1505\u2013\n\t\t\t\t\t1514."},{"issue":"(1)","key":"i1945-7103-92-4-547-b15","series-title":"Biochem J","first-page":"1","article-title":"GSK3 takes centre stage more than 20 years after its discovery","volume":"359","author":"Frame","year":"2001","unstructured":"Frame\n S,\n \n \n Cohen\n P.\n \n \n GSK3 takes centre stage more than 20 years after its discovery.\n\t\t\t\t\tBiochem J.\n\t\t\t\t\t2001;\n\t\t\t\t\t359(1):\n\t\t\t\t\t1\u2013\n\t\t\t\t\t16."},{"issue":"(2)","key":"i1945-7103-92-4-547-b16","series-title":"Bone","first-page":"331","article-title":"Lithium's effect on bone mineral density","volume":"44","author":"Zamani","year":"2009","unstructured":"Zamani\n A,\n \n \n Omrani\n GR,\n \n \n Nasab\n MM.\n \n \n Lithium's effect on bone mineral density.\n\t\t\t\t\tBone.\n\t\t\t\t\t2009;\n\t\t\t\t\t44(2):\n\t\t\t\t\t331\u2013\n\t\t\t\t\t334."},{"issue":"(45)","key":"i1945-7103-92-4-547-b17","series-title":"J Biol Chem","first-page":"39043","article-title":"Inactivation of glycogen synthase kinase-3\u03b2 is required for osteoclast differentiation","volume":"286","author":"Jang","year":"2011","unstructured":"Jang\n HD,\n \n \n Shin\n JH,\n \n \n Park\n DR,\n \n et al.\n \n Inactivation of glycogen synthase kinase-3\u03b2 is required for osteoclast differentiation.\n\t\t\t\t\tJ Biol Chem.\n\t\t\t\t\t2011;\n\t\t\t\t\t286(45):\n\t\t\t\t\t39043\u2013\n\t\t\t\t\t39050."},{"issue":"(3)","key":"i1945-7103-92-4-547-b18","series-title":"Angle Orthod","first-page":"502","article-title":"Force magnitude and duration effects on amount of tooth movement and root resorption in the rat molar","volume":"78","author":"Gonzales","year":"2008","unstructured":"Gonzales\n C,\n \n \n Hotokezaka\n H,\n \n \n Yoshimatsu\n M,\n \n \n Yozgatian\n JH,\n 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CM,\n \n \n Conrad\n LJ,\n \n \n Zhang\n J,\n \n \n Huang\n HC,\n \n \n Lee\n VMY,\n \n \n Klein\n PS.\n \n \n Activation of the Wnt signaling pathway: a molecular mechanism for lithium action.\n\t\t\t\t\tDev Biol.\n\t\t\t\t\t1997;\n\t\t\t\t\t185(1):\n\t\t\t\t\t82\u2013\n\t\t\t\t\t91."},{"issue":"(4)","key":"i1945-7103-92-4-547-b21","series-title":"Biochem Pharmacol","first-page":"397","article-title":"Acceleration of bone regeneration by local application of lithium: Wnt signal-mediated osteoblastogenesis and Wnt signal-independent suppression of osteoclastogenesis","volume":"90","author":"Arioka","year":"2014","unstructured":"Arioka\n M,\n \n \n Takahashi-Yanaga\n F,\n \n \n Sasaki\n M,\n \n et al.\n \n Acceleration of bone regeneration by local application of lithium: Wnt signal-mediated osteoblastogenesis and Wnt signal-independent suppression of osteoclastogenesis.\n\t\t\t\t\tBiochem 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Orthod.\n\t\t\t\t\t1982;\n\t\t\t\t\t52(3):\n\t\t\t\t\t235\u2013\n\t\t\t\t\t258."},{"key":"i1945-7103-92-4-547-b02","series-title":"Nordisk Tandl\u00e4kare Tidskrift","first-page":"236","article-title":"Einige Beitr\u00e4ge zur Theorie der Zahnregulierung","volume":"5","author":"Sandstedt","year":"1904","unstructured":"Sandstedt\n C.\n \n \n Einige Beitr\u00e4ge zur Theorie der Zahnregulierung.\n\t\t\t\t\tNordisk Tandl\u00e4kare Tidskrift.\n\t\t\t\t\t1904;\n\t\t\t\t\t5:\n\t\t\t\t\t236\u2013\n\t\t\t\t\t256."},{"issue":"(2)","key":"i1945-7103-92-4-547-b03","series-title":"J Dent Res","first-page":"145","article-title":"Cellular and molecular pathways leading to external root resorption","volume":"96","author":"Iglesias-Linares","year":"2017","unstructured":"Iglesias-Linares\n A,\n \n \n Hartsfield\n JK.\n \n \n Cellular and molecular pathways leading to external root resorption.\n\t\t\t\t\tJ Dent Res.\n\t\t\t\t\t2017;\n\t\t\t\t\t96(2):\n\t\t\t\t\t145\u2013\n\t\t\t\t\t152."},{"issue":"(4)","key":"i1945-7103-92-4-547-b04","series-title":"Eur J Orthod","first-page":"249","article-title":"Root resorption beneath the main hyalinized zone","volume":"16","author":"Brudvik","year":"1994","unstructured":"Brudvik\n P,\n \n \n Rygh\n P.\n \n \n Root resorption beneath the main hyalinized zone.\n\t\t\t\t\tEur J Orthod.\n\t\t\t\t\t1994;\n\t\t\t\t\t16(4):\n\t\t\t\t\t249\u2013\n\t\t\t\t\t263."},{"issue":"(4)","key":"i1945-7103-92-4-547-b05","series-title":"Eur J Orthod","first-page":"249","article-title":"The initial phase of orthodontic root resorption incident to local compression of the periodontal ligament","volume":"15","author":"Brudvik","year":"1993","unstructured":"Brudvik\n P,\n \n \n Rygh\n P.\n \n \n The initial phase of orthodontic root resorption incident to local compression of the periodontal ligament.\n\t\t\t\t\tEur J Orthod.\n\t\t\t\t\t1993;\n\t\t\t\t\t15(4):\n\t\t\t\t\t249\u2013\n\t\t\t\t\t263."},{"issue":"(4)","key":"i1945-7103-92-4-547-b06","series-title":"Eur J Orthod","first-page":"346","article-title":"Effects of systemic medication on root resorption associated with orthodontic tooth movement: a systematic review of animal studies","volume":"41","author":"Makrygiannakis","year":"2019","unstructured":"Makrygiannakis\n MA,\n \n \n Kaklamanos\n EG,\n \n \n Athanasiou\n AE.\n \n \n Effects of systemic medication on root resorption associated with orthodontic tooth movement: a systematic review of animal studies.\n\t\t\t\t\tEur J Orthod.\n\t\t\t\t\t2019;\n\t\t\t\t\t41(4):\n\t\t\t\t\t346\u2013\n\t\t\t\t\t359."},{"issue":"(2)","key":"i1945-7103-92-4-547-b07","series-title":"Exp Ther Med","first-page":"468","article-title":"Lithium chloride attenuates root resorption during orthodontic tooth movement in rats","volume":"7","author":"Wang","year":"2014","unstructured":"Wang\n Y,\n \n \n Gao\n S,\n \n \n Jiang\n H,\n \n \n Lin\n P,\n \n \n Bao\n X.\n \n \n Lithium chloride attenuates root resorption during orthodontic tooth movement in rats.\n\t\t\t\t\tExp Ther Med.\n\t\t\t\t\t2014;\n\t\t\t\t\t7(2):\n\t\t\t\t\t468\u2013\n\t\t\t\t\t472."},{"issue":"(4)","key":"i1945-7103-92-4-547-b08","series-title":"Angle Orthod","first-page":"474","article-title":"Lithium chloride reduces orthodontically induced root resorption and affects tooth root movement in rats","volume":"88","author":"Ino-Kondo","year":"2018","unstructured":"Ino-Kondo\n A,\n \n \n Hotokezaka\n H,\n \n \n Kondo\n T,\n \n et al.\n \n Lithium chloride reduces orthodontically induced root resorption and affects tooth root movement in rats.\n\t\t\t\t\tAngle Orthod.\n\t\t\t\t\t2018;\n\t\t\t\t\t88(4):\n\t\t\t\t\t474\u2013\n\t\t\t\t\t482."},{"issue":"(9)","key":"i1945-7103-92-4-547-b09","series-title":"Trends Pharmacol Sci","first-page":"441","article-title":"Lithium and GSK-3: one inhibitor, two inhibitory actions, multiple outcomes","volume":"24","author":"Jope","year":"2003","unstructured":"Jope\n RS.\n \n \n Lithium and GSK-3: one inhibitor, two inhibitory actions, multiple outcomes.\n\t\t\t\t\tTrends Pharmacol Sci.\n\t\t\t\t\t2003;\n\t\t\t\t\t24(9):\n\t\t\t\t\t441\u2013\n\t\t\t\t\t443."},{"issue":"(6)","key":"i1945-7103-92-4-547-b10","series-title":"Nat Rev Drug Discov","first-page":"479","article-title":"GSK3 inhibitors: development and therapeutic potential","volume":"3","author":"Cohen","year":"2004","unstructured":"Cohen\n P,\n \n \n Goedert\n M.\n \n \n GSK3 inhibitors: development and therapeutic potential.\n\t\t\t\t\tNat Rev Drug Discov.\n\t\t\t\t\t2004;\n\t\t\t\t\t3(6):\n\t\t\t\t\t479\u2013\n\t\t\t\t\t487."},{"issue":"(10)","key":"i1945-7103-92-4-547-b11","series-title":"Nat Rev Mol Cell Biol","first-page":"769","article-title":"The renaissance of GSK3","volume":"2","author":"Cohen","year":"2001","unstructured":"Cohen\n P,\n \n \n Frame\n S.\n \n \n The renaissance of GSK3.\n\t\t\t\t\tNat Rev Mol Cell Biol.\n\t\t\t\t\t2001;\n\t\t\t\t\t2(10):\n\t\t\t\t\t769\u2013\n\t\t\t\t\t776."},{"issue":"(7)","key":"i1945-7103-92-4-547-b12","series-title":"Cell Death Dis","first-page":"1","article-title":"Lithium reduces apoptosis and autophagy after neonatal hypoxia-ischemia","volume":"1","author":"Li","year":"2010","unstructured":"Li\n Q,\n \n \n Li\n H,\n \n \n Roughton\n K,\n \n \n Wang\n X,\n \n \n Kroemer\n G,\n \n \n Blomgren\n K,\n \n \n Zhu\n C.\n \n \n Lithium reduces apoptosis and autophagy after neonatal hypoxia-ischemia.\n\t\t\t\t\tCell Death Dis.\n\t\t\t\t\t2010;\n\t\t\t\t\t1(7):\n\t\t\t\t\t1\u2013\n\t\t\t\t\t9."},{"issue":"(4)","key":"i1945-7103-92-4-547-b13","series-title":"Cell Death Dis","first-page":"1","article-title":"GSK-3\u03b2-dependent downregulation of \u03b3-taxilin and \u03b1NAC merge to regulate ER stress responses","volume":"6","author":"Hotokezaka","year":"2015","unstructured":"Hotokezaka\n Y,\n \n \n Katayama\n I,\n \n \n Van Leyen\n K,\n \n \n Nakamura\n 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