{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T18:44:34Z","timestamp":1793472274616,"version":"4.5.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Vitamin D and thyroid hormones have crucial roles in bone metabolism. This study aims to explore the effects of vitamin D on bone metabolism in mice with thyrotoxicosis and its mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>12-week-old mice were randomly divided into 6 groups (6 mice\/group), the control (CON) group, vitamin D (VD) group, low-dose LT4 (Low LT4) group, low-dose LT4+VD (Low LT4+VD) group, high-dose LT4 (High LT4) group, high-dose LT4+VD (High LT4+VD) group, LT4 was provided every day and vitamin D3 every other day for 12 weeks. Thyroid function, 25-hydroxy vitamin D, type I collagen carboxy-terminal peptide (CTX), and type I procollagen amino-terminal peptide were determined. In addition, microcomputed tomography, bone histology and histomorphometry, a three-point bending test, and the mRNA expression of osteoprotegerin (OPG), receptor activator of nuclear factor-\u03baB ligand (RANKL) and \u03b2-catenin in bone were conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The BMD of lumbar vertebrae and femur decreased and the bone microstructure was destroyed significantly in thyrotoxicosis mice. Addition of vitamin D improved the BMD and bone microstructure only in the low LT4+VD group. Mice with thyrotoxicosis had a significantly higher level of CTX (<jats:italic>P<\/jats:italic>&amp;lt;0.05), which was decreased by treatment with vitamin D (<jats:italic>P<\/jats:italic>&amp;lt;0.05). The eroded surface per bone surface (Er. S\/BS) of the cancellous bone and elongated surface\/endocortical perimeter (Er. S\/E Pm) of the cortical bone significantly increased in the Low LT4 and High LT4 groups (<jats:italic>P<\/jats:italic>&amp;lt;0.05). Treatment with vitamin D significantly decreased the Er. S\/BS and Er. S\/E Pm. But, treatment with vitamin D did not significantly improve the toughness and rigidity of bones. The ratio of OPG to RANKL and mRNA expression of \u03b2-catenin in the Low LT4+VD group were higher than that in the Low LT4 group (<jats:italic>P<\/jats:italic>&amp;lt;0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In mice with thyrotoxicosis, treatment with vitamin D can inhibit bone resorption and improve the BMD and trabecular bone architecture by increasing the ratio of OPG to RANKL and upregulating the expression of Wnt\/\u03b2-catenin.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.1066089","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T10:57:36Z","timestamp":1669805856000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Vitamin D inhibits bone loss in mice with thyrotoxicosis by activating the OPG\/RANKL and Wnt\/\u03b2-catenin signaling pathways"],"prefix":"10.3389","volume":"13","author":[{"given":"Dan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Jiao","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Yan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Ming","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Jie","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09185-4","article-title":"A systematic review on the definition of rhabdomyolysis","volume":"267","author":"Stahl","year":"2020","journal-title":"J Neurol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.5161","article-title":"Subclinical thyroid dysfunction and fracture risk: a meta-analysis","volume":"313","author":"Blum","year":"2015","journal-title":"Jama"},{"key":"B3","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1002\/wdev.159","article-title":"WNT signaling in bone development and homeostasis","volume":"3","author":"Zhong","year":"2014","journal-title":"Wiley Interdiscip Rev Dev Biol"},{"key":"B4","article-title":"Rank\/Rankl\/opg: literature review","volume":"36","author":"Silva","year":"2011","journal-title":"Acta Reumatol Port"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2008.03.027","article-title":"Osteoclast-osteoblast communication","volume":"473","author":"Matsuo","year":"2008","journal-title":"Arch Biochem Biophys"},{"key":"B6","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1007\/s11914-007-0024-y","article-title":"The RANKL\/RANK\/OPG pathway","volume":"5","author":"Boyce","year":"2007","journal-title":"Curr Osteoporos Rep"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1177\/1087057116654657","article-title":"Development of a high-throughput screening strategy for upregulators of the OPG\/RANKL ratio with the potential for antiosteoporosis effects","volume":"21","author":"Gong","year":"2016","journal-title":"J Biomol Screen"},{"key":"B8","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.taap.2018.02.015","article-title":"Ghrelin protects against depleted uranium-induced bone damage by increasing osteoprotegerin\/RANKL ratio","volume":"343","author":"Hao","year":"2018","journal-title":"Toxicol Appl Pharmacol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3074","article-title":"WNT signaling in bone homeostasis and disease: from human mutations to treatments","volume":"19","author":"Baron","year":"2013","journal-title":"Nat Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2006.01.001","article-title":"A wnt canon orchestrating osteoblastogenesis","volume":"16","author":"Hartmann","year":"2006","journal-title":"Trends Cell Biol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1089\/thy.1999.9.871","article-title":"Special features of graves' disease in early childhood","volume":"9","author":"Segni","year":"1999","journal-title":"Thyroid"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2011.11.002","article-title":"Thyroid hormone metabolism in skeletal development and adult bone maintenance","volume":"23","author":"Waung","year":"2012","journal-title":"Trends Endocrinol Metab"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1136\/pmj.76.899.529","article-title":"Thyroid disorders\u2013an update","volume":"76","author":"Lazarus","year":"2000","journal-title":"Postgrad Med J"},{"key":"B14","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1089\/thy.1999.9.871","article-title":"And bone health: Epidemiologic studies","volume":"3","author":"Ebeling PR. 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