{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T03:47:55Z","timestamp":1752551275516,"version":"3.37.3"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T00:00:00Z","timestamp":1532908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T00:00:00Z","timestamp":1532908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T00:00:00Z","timestamp":1532908800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,11,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Increased intake of vitamin A (retinoids) is associated with decreased bone mass and increased fracture risk in humans. Mechanistic studies in rodents have shown that hypervitaminosis A results in decreased bone mass caused by an increase in periosteal osteoclasts while simultaneously decreasing endocortic osteoclasts. In vivo and ex vivo bone organ cultures have demonstrated that excess retinoids increase osteoclast formation due to increased receptor activator of nuclear factor kappa B-ligand (RANKL) expression. In vitro, studies using murine bone marrow macrophages (BMM) have shown that retinoids inhibit osteoclast formation induced by recombinant RANKL. These opposing in vivo\/ex vivo versus in vitro effects may elucidate why excess retinoids affect periosteal and endocortic osteoclast formation differently. In addition, it has been reported that retinoids can inhibit osteoclast formation under inflammatory conditions such as experimentally induced arthritis in mice. In the present study, we have compared the effect of all-trans-retinoic acid (ATRA) on physiologically and inflammatory induced osteoclastogenesis. ATRA inhibited physiologically induced (RANKL) osteoclast formation of human peripheral blood monocytes and mouse BMM as well as human monocytes stimulated with the pro-inflammatory compounds, TNF-\u03b1 and LPS. The inhibition was due to impeded differentiation, rather than fusion, of mononucleated progenitor cells. ATRA disrupted differentiation by interfering with osteoclastogenic intracellular signaling. In line with this view, overexpression of Tnfrsf11a (encodes for RANK) in BMM could not overcome the inhibition of osteoclastogenesis by ATRA. The data suggest that ATRA inhibits both physiologic and inflammatory osteoclast differentiation of progenitors from the bone marrow and peripheral blood.<\/jats:p>\n               <jats:p>Retinol inhibits physiological and inflammatory induced osteoclastogenesis in vitro through RAR\u03b1 due to the inhibition of differentiation of mononucleated progenitor cells.<\/jats:p>","DOI":"10.1002\/jlb.3a0318-094rr","type":"journal-article","created":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T13:45:18Z","timestamp":1532958318000},"page":"1133-1145","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of retinoids on physiologic and inflammatory osteoclastogenesis in vitro"],"prefix":"10.1093","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1605-3046","authenticated-orcid":false,"given":"Vikte","family":"Lionikaite","sequence":"first","affiliation":[{"name":"Centre for Bone and Arthritis Research at Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Westerlund","sequence":"additional","affiliation":[{"name":"Centre for Bone and Arthritis Research at Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H Herschel","family":"Conaway","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Arkansas for Medical Sciences , Little Rock, Arkansas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Henning","sequence":"additional","affiliation":[{"name":"Centre for Bone and Arthritis Research at Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulf H","family":"Lerner","sequence":"additional","affiliation":[{"name":"Centre for Bone and Arthritis Research at Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,7,30]]},"reference":[{"key":"2023032406073820100_jlb10208-cit-0001","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1210\/er.2012-1071","article-title":"Vitamin A metabolism, action, and role in skeletal homeostasis","volume":"34","author":"Conaway","year":"2013","journal-title":"Endocr Rev"},{"key":"2023032406073820100_jlb10208-cit-0002","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3389\/fendo.2015.00031","article-title":"Retinoid receptors in bone and their role in bone remodeling","volume":"6","author":"Henning","year":"2015","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2023032406073820100_jlb10208-cit-0003","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1210\/me.2014-1316","article-title":"Minireview: nuclear receptor regulation of osteoclast and bone remodeling","volume":"29","author":"Jin","year":"2015","journal-title":"Mol Endocrinol"},{"issue":"Pt A","key":"2023032406073820100_jlb10208-cit-0004","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jsbmb.2015.09.036","article-title":"The role of vitamin A and retinoic acid receptor signaling in post-natal maintenance of bone","volume":"155","author":"Green","year":"2016","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2023032406073820100_jlb10208-cit-0005","doi-asserted-by":"crossref","first-page":"770","DOI":"10.7326\/0003-4819-129-10-199811150-00003","article-title":"Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture","volume":"129","author":"Melhus","year":"1998","journal-title":"Ann Intern Med"},{"key":"2023032406073820100_jlb10208-cit-0006","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1056\/NEJMoa021171","article-title":"Serum retinol levels and the risk of fracture","volume":"348","author":"Michaelsson","year":"2003","journal-title":"N Engl J Med"},{"key":"2023032406073820100_jlb10208-cit-0007","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1002\/jbmr.2237","article-title":"The relationship between vitamin a and risk of fracture: meta-analysis of prospective studies","volume":"29","author":"Wu","year":"2014","journal-title":"J Bone Miner Res"},{"key":"2023032406073820100_jlb10208-cit-0008","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1172\/JCI113257","article-title":"Hypercalcemia induced with an arotinoid in thyroparathyroidectomized rats. 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