{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T11:25:02Z","timestamp":1766575502220,"version":"3.48.0"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K10397"],"award-info":[{"award-number":["19K10397"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K10236"],"award-info":[{"award-number":["22K10236"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"JST SPRING","doi-asserted-by":"publisher","award":["JPMJSP2114"],"award-info":[{"award-number":["JPMJSP2114"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) promotes insulin secretion, lowers blood glucose levels, and is increasingly linked to bone remodeling. Native GIP is quickly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4), whereas (D-Ala2)GIP is a novel GIP analog engineered to resist DPP-4 degradation. Tumor necrosis factor-alpha (TNF-\u03b1), a key proinflammatory cytokine, promotes osteoclastogenesis and is notably upregulated during orthodontic tooth movement (OTM). This study aimed to evaluate the effects of (D-Ala2)GIP on TNF-\u03b1-induced osteoclast formation and bone resorption in vivo, as well as on OTM and related root resorption. Mice received daily supracalvarial injections of TNF-\u03b1 with or without (D-Ala2)GIP for 5 days. The (D-Ala2)GIP-treated group showed significantly reduced osteoclast formation, bone resorption, and expression of osteoclastic markers TRAP and cathepsin K, compared to the group that received TNF-\u03b1 alone. OTM was induced in mice by applying a nickel-titanium closed-coil spring, and mice were treated with either phosphate-buffered saline (PBS) or (D-Ala2)GIP every 2 days. After 12 days, the (D-Ala2)GIP-treated group showed significantly reduced tooth movement and fewer osteoclasts and odontoclasts on the compression side compared to the PBS control. These findings suggest that (D-Ala2)GIP inhibits OTM, potentially by suppressing TNF-\u03b1-driven osteoclastogenesis and bone resorption.<\/jats:p>","DOI":"10.3390\/ijms27010199","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T11:22:14Z","timestamp":1766575334000},"page":"199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["(D-Ala2)GIP Inhibits TNF-\u03b1-Induced Osteoclast Formation and Bone Resorption, and Orthodontic Tooth Movement"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8053-0858","authenticated-orcid":false,"given":"Angyi","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-Machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3249-4247","authenticated-orcid":false,"given":"Hideki","family":"Kitaura","sequence":"additional","affiliation":[{"name":"Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-Machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinghan","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-Machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumitoshi","family":"Ohori","sequence":"additional","affiliation":[{"name":"Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-Machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4324-3155","authenticated-orcid":false,"given":"Aseel","family":"Marahleh","sequence":"additional","affiliation":[{"name":"Creative Interdisciplinary Research Division, Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8578, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayoko","family":"Kanou","sequence":"additional","affiliation":[{"name":"Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-Machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohei","family":"Narita","sequence":"additional","affiliation":[{"name":"Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-Machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8940-4979","authenticated-orcid":false,"given":"Ziqiu","family":"Fan","sequence":"additional","affiliation":[{"name":"Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-Machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kou","family":"Murakami","sequence":"additional","affiliation":[{"name":"Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-Machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyasu","family":"Kanetaka","sequence":"additional","affiliation":[{"name":"Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-Machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan"},{"name":"Division of Advanced Dental Science and Technology, Graduate School of Biomedical Engineering, Tohoku University, 6-6-12, Aramaki Aza Aoba, Aoba-ku, Sendai 980-8579, Miyagi, Japan"},{"name":"Liaison Center for Innovative Dentistry, Division of Interdisciplinary Co-Creation (ICC-Division), Tohoku University Graduate School of Dentistry, 4-1 Seiryo-Machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2009). Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, 32, S62\u2013S67.","DOI":"10.2337\/dc09-S062"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1021\/jm0306273","article-title":"Diabetes Mellitus: Pathogenesis and Treatment Strategies","volume":"47","author":"Skyler","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tiwari, P. (2015). Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update. J. Diabetes Res., 2015.","DOI":"10.1155\/2015\/340838"},{"key":"ref_4","unstructured":"GBD 2021 Diabetes Collaborators (2023). Global, Regional, and National Burden of Diabetes from 1990 to 2021, with Projections of Prevalence to 2050: A Systematic Analysis for the Global Burden of Disease Study 2021. Lancet, 402, 203\u2013234."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1016\/S0168-8227(11)70011-0","article-title":"Incretin Effect: GLP-1, GIP, DPP4","volume":"93","author":"Kazakos","year":"2011","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Edholm, T., Degerblad, M., Gryb\u00e4ck, P., Hilsted, L., Holst, J.J., Jacobsson, H., Efendic, S., Schmidt, P.T., and Hellstr\u00f6m, P.M. (2010). Differential Incretin Effects of GIP and GLP-1 on Gastric Emptying, Appetite, and Insulin-Glucose Homeostasis: Incretins, Gastric Emptying and Metabolic Control. Neurogastroenterol. Motil., 22.","DOI":"10.1111\/j.1365-2982.2010.01554.x"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.2040-1124.2010.00022.x","article-title":"GIP and GLP-1, the Two Incretin Hormones: Similarities and Differences","volume":"1","author":"Seino","year":"2010","journal-title":"J. Diabetes Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.pbiomolbio.2011.07.010","article-title":"Two Incretin Hormones GLP-1 and GIP: Comparison of Their Actions in Insulin Secretion and \u03b2 Cell Preservation","volume":"107","author":"Yabe","year":"2011","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1111\/j.1432-1033.1993.tb17986.x","article-title":"Dipeptidyl-Peptidase IV Hydrolyses Gastric Inhibitory Polypeptide, Glucagon-like Peptide-1(7\u201336)Amide, Peptide Histidine Methionine and Is Responsible for Their Degradation in Human Serum","volume":"214","author":"Mentlein","year":"1993","journal-title":"Eur. J. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3585","DOI":"10.1210\/endo.136.8.7628397","article-title":"Degradation of Glucose-Dependent Insulinotropic Polypeptide and Truncated Glucagon-like Peptide 1 in Vitro and in Vivo by Dipeptidyl Peptidase IV","volume":"136","author":"Kieffer","year":"1995","journal-title":"Endocrinology"},{"key":"ref_11","first-page":"187","article-title":"Analogs of Glucose-Dependent Insulinotropic Polypeptide with Increased Dipeptidyl Peptidase IV Resistance","volume":"477","author":"Manhart","year":"2000","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"652","DOI":"10.2337\/diabetes.51.3.652","article-title":"Dipeptidyl Peptidase IV-Resistant [D-Ala2]Glucose-Dependent Insulinotropic Polypeptide (GIP) Improves Glucose Tolerance in Normal and Obese Diabetic Rats","volume":"51","author":"Hinke","year":"2002","journal-title":"Diabetes"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"25103","DOI":"10.1074\/jbc.R109.041087","article-title":"Cellular and Molecular Mechanisms of Bone Remodeling","volume":"285","author":"Raggatt","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1152\/physiol.00061.2014","article-title":"Physiological Bone Remodeling: Systemic Regulation and Growth Factor Involvement","volume":"31","author":"Siddiqui","year":"2016","journal-title":"Physiology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yahara, Y., Nguyen, T., Ishikawa, K., Kamei, K., and Alman, B.A. (2022). The Origins and Roles of Osteoclasts in Bone Development, Homeostasis and Repair. Development, 149.","DOI":"10.1242\/dev.199908"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Schiellerup, S.P., Skov-Jeppesen, K., Windel\u00f8v, J.A., Svane, M.S., Holst, J.J., Hartmann, B., and Rosenkilde, M.M. (2019). Gut Hormones and Their Effect on Bone Metabolism. Potential Drug Therapies in Future Osteoporosis Treatment. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00075"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Stensen, S., Gasbjerg, L.S., Helsted, M.M., Hartmann, B., Christensen, M.B., and Knop, F.K. (2020). GIP and the Gut-Bone Axis\u2013Physiological, Pathophysiological and Potential Therapeutic Implications. Peptides, 125.","DOI":"10.1016\/j.peptides.2019.170197"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E543","DOI":"10.1152\/ajpendo.00364.2006","article-title":"Effects of Glucose-Dependent Insulinotropic Peptide on Osteoclast Function","volume":"292","author":"Zhong","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1210\/endo.141.3.7366","article-title":"Osteoblast-Derived Cells Express Functional Glucose- Dependent Insulinotropic Peptide Receptors","volume":"141","author":"Bollag","year":"2000","journal-title":"Endocrinology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1093\/ejendo\/lvac004","article-title":"GIP Reduces Osteoclast Activity and Improves Osteoblast Survival in Primary Human Bone Cells","volume":"188","author":"Hansen","year":"2023","journal-title":"Eur. J. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1210\/jc.2017-01949","article-title":"Glucose-Dependent Insulinotropic Polypeptide (GIP) Inhibits Bone Resorption Independently of Insulin and Glycemia","volume":"103","author":"Christensen","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Christensen, M.B., Lund, A.B., J\u00f8rgensen, N.R., Holst, J.J., Vilsb\u00f8ll, T., and Knop, F.K. (2020). Glucose-Dependent Insulinotropic Polypeptide (GIP) Reduces Bone Resorption in Patients With Type 2 Diabetes. J. Endocr. Soc., 4.","DOI":"10.1210\/jendso\/bvaa097"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E2325","DOI":"10.1210\/jc.2014-2547","article-title":"Glucose-Dependent Insulinotropic Polypeptide Inhibits Bone Resorption in Humans","volume":"99","author":"Nissen","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.bone.2016.07.014","article-title":"Glucose-Dependent Insulinotropic Polypeptide (GIP) Dose-Dependently Reduces Osteoclast Differentiation and Resorption","volume":"91","author":"Mabilleau","year":"2016","journal-title":"Bone"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lin, A., Kitaura, H., Ohori, F., Noguchi, T., Marahleh, A., Ma, J., Ren, J., Miura, M., Fan, Z., and Narita, K. (2024). (D-Ala2)GIP Inhibits Inflammatory Bone Resorption by Suppressing TNF-\u03b1 and RANKL Expression and Directly Impeding Osteoclast Formation. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052555"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.cytogfr.2014.07.016","article-title":"TNF and TNF-Receptors: From Mediators of Cell Death and Inflammation to Therapeutic Giants\u2013Past, Present and Future","volume":"25","author":"Sedger","year":"2014","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Gough, P., and Myles, I.A. (2020). Tumor Necrosis Factor Receptors: Pleiotropic Signaling Complexes and Their Differential Effects. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.585880"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1084\/jem.191.2.275","article-title":"Tumor Necrosis Factor \u03b1 Stimulates Osteoclast Differentiation by a Mechanism Independent of the ODF\/RANKL\u2013RANK Interaction","volume":"191","author":"Kobayashi","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kitaura, H., Marahleh, A., Ohori, F., Noguchi, T., Nara, Y., Pramusita, A., Kinjo, R., Ma, J., Kanou, K., and Mizoguchi, I. (2022). Role of the Interaction of Tumor Necrosis Factor-\u03b1 and Tumor Necrosis Factor Receptors 1 and 2 in Bone-Related Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031481"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Marahleh, A., Kitaura, H., Ohori, F., Noguchi, T., and Mizoguchi, I. (2023). The Osteocyte and Its Osteoclastogenic Potential. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1121727"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/icb.2013.15","article-title":"Regulation of TNF-\u03b1 with a Focus on Rheumatoid Arthritis","volume":"91","author":"Moelants","year":"2013","journal-title":"Immunol. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/jre.12339","article-title":"The Effects of Tumour Necrosis Factor-\u03b1 on Bone Cells Involved in Periodontal Alveolar Bone Loss; Osteoclasts, Osteoblasts and Osteocytes","volume":"51","author":"Algate","year":"2016","journal-title":"J. Periodontal Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/ejo\/cjl001","article-title":"The Tissue, Cellular, and Molecular Regulation of Orthodontic Tooth Movement: 100 Years after Carl Sandstedt","volume":"28","author":"Meikle","year":"2005","journal-title":"Eur. J. Orthod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.ajodo.2005.12.013","article-title":"Current Concepts in the Biology of Orthodontic Tooth Movement","volume":"129","author":"Masella","year":"2006","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_35","first-page":"156","article-title":"Mechanobiology of Orthodontic Tooth Movement: An Update","volume":"12","author":"Maltha","year":"2023","journal-title":"J. World Fed. Orthod."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Feller, L., Khammissa, R.A.G., Thomadakis, G., Fourie, J., and Lemmer, J. (2016). Apical External Root Resorption and Repair in Orthodontic Tooth Movement: Biological Events. BioMed Res. Int., 2016.","DOI":"10.1155\/2016\/4864195"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.ajodo.2009.06.021","article-title":"Root Resorption Associated with Orthodontic Tooth Movement: A Systematic Review","volume":"137","author":"Weltman","year":"2010","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/ejo\/16.4.249","article-title":"Root Resorption beneath the Main Hyalinized Zone","volume":"16","author":"Brudvik","year":"1994","journal-title":"Eur. J. Orthod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/jemt.10370","article-title":"Differentiation and Functions of Osteoclasts and Odontoclasts in Mineralized Tissue Resorption","volume":"61","author":"Sasaki","year":"2003","journal-title":"Microsc. Res. Tech."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1177\/00220345960750010801","article-title":"Interleukin (IL)-1\u03b2, IL-6, Tumor Necrosis Factor-\u03b1, Epidermal Growth Factor, and B2-Microglobulin Levels Are Elevated in Gingival Crevicular Fluid during Human Orthodontic Tooth Movement","volume":"75","author":"Uematsu","year":"1996","journal-title":"J. Dent. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s00774-005-0641-4","article-title":"Experimental Model of Tooth Movement by Orthodontic Force in Mice and Its Application to Tumor Necrosis Factor Receptor-Deficient Mice","volume":"24","author":"Yoshimatsu","year":"2005","journal-title":"J. Bone Miner. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.jds.2021.03.006","article-title":"Effect of TNF-\u03b1 on Osteocyte RANKL Expression during Orthodontic Tooth Movement","volume":"16","author":"Marahleh","year":"2021","journal-title":"J. Dent. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1177\/154405910808700405","article-title":"An Anti-c-Fms Antibody Inhibits Orthodontic Tooth Movement","volume":"87","author":"Kitaura","year":"2008","journal-title":"J. Dent. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.jds.2023.09.016","article-title":"Effect of Age on Orthodontic Tooth Movement in Mice","volume":"19","author":"Kanou","year":"2024","journal-title":"J. Dent. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Yamauchi, T., Miyabe, M., Nakamura, N., Ito, M., Sekiya, T., Kanada, S., Hoshino, R., Matsubara, T., Miyazawa, K., and Goto, S. (2022). Impacts of Glucose-Dependent Insulinotropic Polypeptide on Orthodontic Tooth Movement-Induced Bone Remodeling. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23168922"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Helsted, M.M., Gasbjerg, L.S., Lanng, A.R., Bergmann, N.C., Stensen, S., Hartmann, B., Christensen, M.B., Holst, J.J., Vilsb\u00f8ll, T., and Rosenkilde, M.M. (2020). The Role of Endogenous GIP and GLP-1 in Postprandial Bone Homeostasis. Bone, 140.","DOI":"10.1016\/j.bone.2020.115553"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ma, J., Kitaura, H., Ogawa, S., Ohori, F., Noguchi, T., Marahleh, A., Nara, Y., Pramusita, A., Kinjo, R., and Kanou, K. (2023). Docosahexaenoic Acid Inhibits TNF-\u03b1-Induced Osteoclast Formation and Orthodontic Tooth Movement through GPR120. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.929690"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"77","DOI":"10.14740\/jocmr3285w","article-title":"Orthodontic Treatment Consideration in Diabetic Patients","volume":"10","author":"Almadih","year":"2018","journal-title":"J. Clin. Med. Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Nauck, M.A., and D\u2018Alessio, D.A. (2022). Tirzepatide, a Dual GIP\/GLP-1 Receptor Co-Agonist for the Treatment of Type 2 Diabetes with Unmatched Effectiveness Regrading Glycaemic Control and Body Weight Reduction. Cardiovasc. Diabetol., 21.","DOI":"10.1186\/s12933-022-01604-7"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.jds.2024.10.020","article-title":"Exacerbating Orthodontic Tooth Movement in Mice with Salt-Sensitive Hypertension","volume":"20","author":"Fan","year":"2025","journal-title":"J. Dent. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/199\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T11:23:08Z","timestamp":1766575388000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,24]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27010199"],"URL":"https:\/\/doi.org\/10.3390\/ijms27010199","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,24]]}}}