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15-10-2022 | Tooth Extraction | Research

Lithium chloride stimulates bone formation in extraction socket repair in rats

Authors: Poliana Mendes Duarte, Tamires Szeremeske Miranda, Letícia Macedo Marins, João Ricardo Batistão da Silva, Fernando de Souza Malta, Bruno César de Vasconcelos Gurgel, Marcelo Henrique Napimoga

Published in: Oral and Maxillofacial Surgery | Issue 1/2024

Abstract

Purpose

Previous evidence shows that lithium chloride (LiCl), a suppressor of glycogen synthase kinase-3β (GSK-3β), may enhance bone formation in several medical and dental conditions. Thus, the purpose of the current study was to assess the effects of LiCl on extraction socket repair in rats.

Methods

Thirty rats were randomly assigned into a control group (administration of water; n = 15) or a LiCl group (administration of 150 mg/kg of LiCl; n = 15). LiCl and water were given every other day, starting at 7 days before the extraction of upper first molars until the end of each experiment period. Histological sections from five rats per group were obtained at 10, 20, and 30 days post-extractions. Histometrical analysis of newly formed bone (NB) and the levels of tartrate-resistant acid phosphatase (TRAP)-stained cells were evaluated at 10, 20, and 30 days post-extractions. Immunohistochemical staining for receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), bone sialoprotein (BSP), osteocalcin (OCN), and osteopontin (OPN) was assessed at 10 days post-extractions.

Results

The LiCl group had a greater proportion of NB than the control group at 20 days (P < 0.05). At 30 days, the rate of TRAP-stained cells was lower in the LiCl group than in the control group (P < 0.05). At 10 days, the LiCl group presented stronger staining for OPG, BSP, OPN, and OCN, when compared to the control group (P < 0.05).

Conclusion

Systemic LiCl enhanced extraction socket repair, stimulated an overall increase in bone formation markers, and restricted the levels of TRAP in rats.

Felber W, Bauer M, Lewitzka U, Müller-Oerlinghausen B (2018) Lithium clinics in Berlin and Dresden: a 50-year experience. Pharmacopsychiatry 51:166–171. https://doi.org/10.1055/a-0633-3450CrossRefPubMed

Tsaltas E, Kontis D, Boulougouris V, Papadimitriou GN (2009) Lithium and cognitive enhancement: leave it or take it? Psychopharmacology 202:457–476. https://doi.org/10.1007/s00213-008-1241-5CrossRefPubMed

Wong SK, Chin KY, Ima-Nirwana S (2020) The skeletal-protecting action and mechanisms of action for mood-stabilizing drug lithium chloride: current evidence and future potential research areas. Front Pharmacol 11:430. https://doi.org/10.3389/fphar.2020.00430CrossRefPubMedPubMedCentral

Bai J, Xu Y, Dieo Y, Sun G (2019) Combined low-dose LiCl and LY294002 for the treatment of osteoporosis in ovariectomized rats. J Orthop Surg Res 14:177. https://doi.org/10.1186/s13018-019-1210-1CrossRefPubMedPubMedCentral

Tang L, Chen Y, Pei F, Zhang H (2015) Lithium chloride modulates adipogenesis and osteogenesis of human bone marrow-derived mesenchymal stem cells. Cell Physiol Biochem 37:143–152. https://doi.org/10.1159/000430340CrossRefPubMed

Clément-Lacroix P, Ai M, Morvan F, Roman-Roman S, Vayssière B, Belleville C, Estrera K, Warman ML, Baron R, Rawadi G (2005) Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice. Proc Natl Acad Sci U S A 102:17406–17411. https://doi.org/10.1073/pnas.0505259102ADSCrossRefPubMedPubMedCentral

Pan J, He S, Yin X, Li Y, Zhou C, Zou S (2017) Lithium enhances alveolar bone formation during orthodontic retention in rats. Orthod Craniofac Res 20:146–151. https://doi.org/10.1111/ocr.12190CrossRefPubMed

Nordenström J, Elvius M, Bågedahl-Strindlund M, Zhao B, Törring O (1994) Biochemical hyperparathyroidism and bone mineral status in patients treated long-term with lithium. Metabolism 43:1563–1567. https://doi.org/10.1016/0026-0495(94)90017-5CrossRefPubMed

Zamani A, Omrani GR, Nasab MM (2009) Lithium’s effect on bone mineral density. Bone 44:331–334. https://doi.org/10.1016/j.bone.2008.10.001CrossRefPubMed

10.

Bernick J, Wang Y, Sigal IA, Alman BA, Whyne CM, Nam D (2014) Parameters for lithium treatment are critical in its enhancement of fracture-healing in rodents. J Bone Joint Surg Am 96:1990–1998. https://doi.org/10.2106/JBJS.N.00057CrossRefPubMedPubMedCentral

11.

Vachhani K, Pagotto A, Wang Y, Whyne C, Nam D (2018) Design of experiments confirms optimization of lithium administration parameters for enhanced fracture healing. J Biomech 66:153–158. https://doi.org/10.1016/j.jbiomech.2017.09.043CrossRefPubMed

12.

Jin Y, Xu L, Hu X, Liao S, Pathak JL, Liu J (2017) Lithium chloride enhances bone regeneration and implant osseointegration in osteoporotic conditions. J Bone Miner Metab 35:497–503. https://doi.org/10.1007/s00774-016-0783-6CrossRefPubMed

13.

Posch AT, de Avellar-Pinto JF, Malta FS, Marins LM, Teixeira LN, Peruzzo DC, Martinez EF, Clemente-Napimoga JT, Duarte PM, Napimoga MH (2020) Lithium chloride improves bone filling around implants placed in estrogen-deficient rats. Arch Oral Biol 111:104644. https://doi.org/10.1016/j.archoralbio.2019.104644CrossRefPubMed

14.

Ino-Kondo A, Hotokezaka H, Kondo T, Arizono K, Hashimoto M, Hotokezaka Y, Kurohama T, Morita Y, Yoshida N (2018) Lithium chloride reduces orthodontically induced root resorption and affects tooth root movement in rats. Angle Orthod 88:474–482. https://doi.org/10.2319/112017-801.1CrossRefPubMedPubMedCentral

15.

Huang L, Yin X, Chen J, Liu R, Xiao X, Hu Z, He Y, Zou S (2021) Lithium chloride promotes osteogenesis and suppresses apoptosis during orthodontic tooth movement in osteoporotic model via regulating autophagy. Bioact Mater 6:3074–3084. https://doi.org/10.1016/j.bioactmat.2021.02.015CrossRefPubMedPubMedCentral

16.

Tang GH, Xu J, Chen RJ, Qian YF, Shen G (2011) Lithium delivery enhances bone growth during midpalatal expansion. J Dent Res 90:336–340. https://doi.org/10.1177/0022034510389180CrossRefPubMed

17.

Naruse H, Itoh S, Itoh Y, Kagioka T, Abe M, Hayashi M (2021) The Wnt/β-catenin signaling pathway has a healing ability for periapical periodontitis. Sci Rep 11:19673. https://doi.org/10.1038/s41598-021-99231-xADSCrossRefPubMedPubMedCentral

18.

Han P, Ivanovski S, Crawford R, Xiao Y (2015) Activation of the canonical Wnt signaling pathway induces cementum regeneration. J Bone Miner Res 30(7):1160–1174. https://doi.org/10.1002/jbmr.2445CrossRefPubMed

19.

Zeng YT, Fu B, Tang GH, Zhang L, Qian YF (2013) Effects of lithium on extraction socket healing in rats assessed with micro-computed tomography. Acta Odontol Scand 71:1335–1340. https://doi.org/10.3109/00016357.2013.764004CrossRefPubMed

20.

Duarte PM, Miranda TS, Marins LM, Perez EG, Copes LG, Tonietto CB, Montalli VAM, Malta FS, Napimoga MH (2020) Systemic lithium chloride administration improves tooth extraction wound healing in estrogen-deficient rats. Braz Dent J 31:640–649. https://doi.org/10.1590/0103-6440202003595CrossRefPubMed

21.

Bezerra JP, de Siqueira A, Pires AG, Marques MR, Duarte PM, Bastos MF (2013) Effects of estrogen deficiency and/or caffeine intake on alveolar bone loss, density, and healing: a study in rats. J Periodontol 84:839–849. https://doi.org/10.1902/jop.2012.120192CrossRefPubMed

22.

Fedchenko N, Reifenrath J (2014) Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue — a review. Diagn Pathol 9:221. https://doi.org/10.1186/s13000-014-0221-9CrossRefPubMedPubMedCentral

23.

Bord S (2003) Protein localization in wax-embedded and frozen sections of bone using immunohistochemistry. Methods Mol Med 80:237–247. https://doi.org/10.1385/1-59259-366-6:237CrossRefPubMed

24.

Araújo MG, Silva CO, Misawa M (2000) Sukekava F (2015) Alveolar socket healing: what can we learn? Periodontol 68:122–134. https://doi.org/10.1111/prd.12082CrossRef

25.

Hoang QQ, Sicheri F, Howard AJ, Yang DS (2003) Bone recognition mechanism of porcine osteocalcin from crystal structure. Nature 425(6961):977–980. https://doi.org/10.1038/nature02079ADSCrossRefPubMed

26.

Kruger TE, Miller AH, Godwin AK, Wang J (2014) Bone sialoprotein and osteopontin in bone metastasis of osteotropic cancers. Crit Rev Oncol Hematol 89:330–341. https://doi.org/10.1016/j.critrevonc.2013.08.013CrossRefPubMed

27.

Zoch ML, Clemens TL, Riddle RC (2016) New insights into the biology of osteocalcin. Bone 82:42–49. https://doi.org/10.1016/j.bone.2015.05.046CrossRefPubMed

28.

Bailey S, Karsenty G, Gundberg C, Vashishth D (2017) Osteocalcin and osteopontin influence bone morphology and mechanical properties. Ann N Y Acad Sci 1409:79–84. https://doi.org/10.1111/nyas.13470ADSCrossRefPubMedPubMedCentral

29.

Icer MA, Gezmen-Karadag M (2018) The multiple functions and mechanisms of osteopontin. Clin Biochem 59:17–24. https://doi.org/10.1016/j.clinbiochem.2018.07.003CrossRefPubMed

30.

Singh A, Gill G, Kaur H, Amhmed M, Jakhu H (2018) Role of osteopontin in bone remodeling and orthodontic tooth movement: a review. Prog Orthod 19:18. https://doi.org/10.1186/s40510-018-0216-2CrossRefPubMedPubMedCentral

31.

Komori T (2020) Functions of osteocalcin in bone, pancreas, testis, and muscle Int J Mol Sci 21:7513. https://doi.org/10.3390/ijms21207513

32.

Zhang J, Tu Q, Chen J (2009) Applications of transgenics in studies of bone sialoprotein. J Cell Physiol 220:30–34. https://doi.org/10.1002/jcp.21768CrossRefPubMedPubMedCentral

33.

Klein A, Baranowski A, Ritz U, Mack C, Götz H, Langendorf E, Al-Nawas B, Drees P, Rommens PM, Hofmann A (2020) Effect of bone sialoprotein coating on progression of bone formation in a femoral defect model in rats. Eur J Trauma Emerg Surg 46:277–286. https://doi.org/10.1007/s00068-019-01159-5CrossRefPubMed

34.

Boyce BF, Xing L (2008) Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 473:139–146. https://doi.org/10.1016/j.abb.2008.03.018CrossRefPubMedPubMedCentral

35.

Pérez-Sayáns M, Somoza-Martín JM, Barros-Angueira F, Rey JM, García-García A (2010) RANK/RANKL/OPG role in distraction osteogenesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109:679–686. https://doi.org/10.1016/j.tripleo.2009.10.042CrossRefPubMed

36.

Yu Z, Fan L, Li J, Ge Z, Dang X, Wang K (2015) Lithium chloride attenuates the abnormal osteogenic/adipogenic differentiation of bone marrow-derived mesenchymal stem cells obtained from rats with steroid-related osteonecrosis by activating the β-catenin pathway. Int J Mol Med 36:1264–1272. https://doi.org/10.3892/ijmm.2015.2340CrossRefPubMedPubMedCentral

37.

Song H, Deng B, Zou C, Huai W, Zhao R, Zhao W (2015) GSK3β negatively regulates LPS-induced osteopontin expression via inhibiting its transcription. Scand J Immunol 81:186–191. https://doi.org/10.1111/sji.12268CrossRefPubMed

38.

de Souza MF, Napimoga MH, Marins LM, Miranda TS, de Oliveira FB, Posch AT, Feres M, Duarte PM (2020) Lithium chloride assuages bone loss in experimental periodontitis in estrogen-deficient rats. Clin Oral Investig 24:2025–2036. https://doi.org/10.1007/s00784-019-03067-9CrossRef

39.

Hayman AR (2008) Tartrate-resistant acid phosphatase (TRAP) and the osteoclast/immune cell dichotomy. Autoimmunity 41:218–223. https://doi.org/10.1080/08916930701694667CrossRefPubMed

40.

Spencer GJ, Utting JC, Etheridge SL, Arnett TR, Genever PG (2006) Wnt signalling in osteoblasts regulates expression of the receptor activator of NFkappaB ligand and inhibits osteoclastogenesis in vitro. J Cell Sci 119(Pt 7):1283–1296. https://doi.org/10.1242/jcs.02883CrossRefPubMed

41.

Qi J, Hu KS, Yang HL (2015) Roles of TNF-α, GSK-3β and RANKL in the occurrence and development of diabetic osteoporosis. Int J Clin Exp Pathol 8:11995–12004PubMedPubMedCentral

42.

Ek-Rylander B, Andersson G (2010) Osteoclast migration on phosphorylated osteopontin is regulated by endogenous tartrate-resistant acid phosphatase. Exp Cell Res 316:443–451. https://doi.org/10.1016/j.yexcr.2009.10.019CrossRefPubMed

43.

Katoh M, Katoh M (2017) Molecular genetics and targeted therapy of Wnt-related human diseases (review). Int J Mol Med 40:587–606. https://doi.org/10.3892/ijmm.2017.3071CrossRefPubMedPubMedCentral

44.

Huybrechts Y, Mortier G, Boudin E (2020) Van Hul W (2020) Wnt signaling and bone: lessons from skeletal dysplasias and disorders. Front Endocrinol (Lausanne) 11:165. https://doi.org/10.3389/fendo.2020.00165CrossRefPubMed

45.

Klein PS, Melton DA (1996) A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci U S A 93:8455–8459. https://doi.org/10.1073/pnas.93.16.8455ADSCrossRefPubMedPubMedCentral

46.

Fang D, Hawke D, Zheng Y, Xia Y, Meisenhelder J, Nika H, Mills GB, Kobayashi R, Hunter T, Lu Z (2007) Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity. J Biol Chem 282:11221–11229. https://doi.org/10.1074/jbc.M611871200CrossRefPubMed

47.

Zhong Z, Ethen NJ, Williams BO (2014) Wnt signaling in bone development and homeostasis. Wiley Interdiscip Rev Dev Biol 3:489–500. https://doi.org/10.1002/wdev.159CrossRefPubMedPubMedCentral

48.

Livingstone C (2006) Rampes H (2006) Lithium: a review of its metabolic adverse effects. J Psychopharmacol 20:347–355. https://doi.org/10.1177/0269881105057515CrossRefPubMed

Title: Lithium chloride stimulates bone formation in extraction socket repair in rats
Authors: Poliana Mendes Duarte
Tamires Szeremeske Miranda
Letícia Macedo Marins
João Ricardo Batistão da Silva
Fernando de Souza Malta
Bruno César de Vasconcelos Gurgel
Marcelo Henrique Napimoga
Publication date: 15-10-2022
Publisher: Springer Berlin Heidelberg
Keywords: Tooth Extraction
Tooth Extraction
Published in: Oral and Maxillofacial Surgery / Issue 1/2024
Print ISSN: 1865-1550
Electronic ISSN: 1865-1569
DOI: https://doi.org/10.1007/s10006-022-01124-4

2024 ASCO Annual Meeting

Springer Medicine

Lithium chloride stimulates bone formation in extraction socket repair in rats

Abstract

Purpose

Methods

Results

Conclusion

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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