{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:03:28Z","timestamp":1783112608883,"version":"3.54.6"},"reference-count":127,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"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":["25K02830"],"award-info":[{"award-number":["25K02830"]}],"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>Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin hormone identified, best known for promoting glucose-stimulated insulin secretion. Increasing evidence has expanded its physiological relevance beyond glucose metabolism, revealing a significant role for GIP in the gut\u2013bone axis. In vitro studies demonstrate that GIP inhibits osteoclast differentiation and activity while promoting osteoblastic bone formation. Findings from genetic animal models and human variant analyses further support the essential role of endogenous GIP signaling in maintaining bone mass and quality. Exogenous administration of GIP suppresses the bone-resorption marker C-terminal telopeptide of type I collagen (CTX) and increases the bone-formation marker procollagen type I N-terminal propeptide (P1NP) in healthy individuals, reflecting an acute shift toward reduced bone resorption and enhanced bone formation. Moreover, GIP confers protection against bone deterioration in multiple pathological conditions, including postmenopausal osteoporosis, inflammatory bone loss, obesity, and diabetes, etc., suggesting therapeutic potential beyond physiological contexts. Recent evidence also shows that GIP attenuates orthodontic tooth movement by limiting mechanically induced osteoclast activity, highlighting its broader skeletal actions. In this review, we summarize recent advances regarding the role of GIP in bone metabolism, integrating evidence from cellular studies, animal models and human investigations, and discuss future directions for GIP-based interventions.<\/jats:p>","DOI":"10.3390\/ijms27020600","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T09:34:12Z","timestamp":1767778452000},"page":"600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Role of Glucose-Dependent Insulinotropic Polypeptide (GIP) in Bone Metabolism"],"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":"Division of Interdisciplinary Co-Creation (ICC-Division), Liaison Center for Innovative Dentistry, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-Machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102118","DOI":"10.1016\/j.molmet.2025.102118","article-title":"Glucose-Dependent Insulinotropic Polypeptide (GIP)","volume":"95","author":"Adriaenssens","year":"2025","journal-title":"Mol. 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