{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:15Z","timestamp":1784557215741,"version":"3.55.0"},"reference-count":33,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,5]]},"abstract":"\n Substantial progress has been made in the therapeutic reduction of vertebral fracture risk in patients with osteoporosis, but non-vertebral fracture risk has been improved only marginally. Human genetic studies demonstrate that the\n WNT16<\/jats:italic>\n locus is a major determinant of cortical bone thickness and non-vertebral fracture risk and mouse models with life-long\n Wnt16<\/jats:italic>\n inactivation revealed that WNT16 is a key regulator of cortical thickness. These studies, however, could not exclude that the effect of\n Wnt16<\/jats:italic>\n inactivation on cortical thickness might be caused by early developmental and\/or growth effects. To determine the effect of WNT16 specifically on adult cortical bone homeostasis,\n Wnt16<\/jats:italic>\n was conditionally ablated in young adult and old mice through tamoxifen-inducible Cre-mediated recombination using CAG-Cre-ER;\n Wnt16<\/jats:italic>\n flox\/flox<\/jats:sup>\n (\n Cre-Wnt16<\/jats:italic>\n flox\/flox<\/jats:sup>\n ) mice. First, 10-week-old\n Cre-Wnt16<\/jats:italic>\n flox\/flox<\/jats:sup>\n and\n Wnt16<\/jats:italic>\n flox\/flox<\/jats:sup>\n littermate control mice were treated with tamoxifen. Four weeks later,\n Wnt16<\/jats:italic>\n mRNA levels in cortical bone were reduced and cortical thickness in femur was decreased in\n Cre-Wnt16<\/jats:italic>\n flox\/flox<\/jats:sup>\n mice compared to\n Wnt16<\/jats:italic>\n flox\/flox<\/jats:sup>\n mice. Then, inactivation of\n Wnt16<\/jats:italic>\n in 47-week-old mice (evaluated four weeks later) resulted in a reduction of\n Wnt16<\/jats:italic>\n mRNA levels, cortical thickness and cortical bone strength with no effect on trabecular bone volume fraction. Mechanistic studies demonstrated that the reduced cortical bone thickness was caused by a combination of increased bone resorption and reduced periosteal bone formation. In conclusion, WNT16 is a crucial regulator of cortical bone thickness in young adult and old mice. We propose that new treatment strategies targeting the adult regulation of WNT16 might be useful to reduce fracture risk at cortical bone sites.\n <\/jats:p>","DOI":"10.1530\/joe-18-0020","type":"journal-article","created":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T20:10:44Z","timestamp":1520885444000},"page":"113-122","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":36,"title":["Inducible Wnt16 inactivation: WNT16 regulates cortical bone thickness in adult mice"],"prefix":"10.1530","volume":"237","author":[{"given":"Claes","family":"Ohlsson","sequence":"first","affiliation":[{"name":"1Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Henning","sequence":"additional","affiliation":[{"name":"1Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin H","family":"Nilsson","sequence":"additional","affiliation":[{"name":"1Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyao","family":"Wu","sequence":"additional","affiliation":[{"name":"1Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin L","family":"Gustafsson","sequence":"additional","affiliation":[{"name":"1Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Sj\u00f6gren","sequence":"additional","affiliation":[{"name":"1Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"T\u00f6rnqvist","sequence":"additional","affiliation":[{"name":"1Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Koskela","sequence":"additional","affiliation":[{"name":"2Department of Anatomy and Cell Biology, Institute of Cancer Research and Translational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Ping","family":"Zhang","sequence":"additional","affiliation":[{"name":"3Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie K","family":"Lagerquist","sequence":"additional","affiliation":[{"name":"1Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Poutanen","sequence":"additional","affiliation":[{"name":"1Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden"},{"name":"3Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Tuukkanen","sequence":"additional","affiliation":[{"name":"2Department of Anatomy and Cell Biology, Institute of Cancer Research and Translational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf H","family":"Lerner","sequence":"additional","affiliation":[{"name":"1Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Mov\u00e9rare-Skrtic","sequence":"additional","affiliation":[{"name":"1Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, 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