{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T15:49:17Z","timestamp":1769874557061,"version":"3.49.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005760","name":"University of Gothenburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005760","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Calcif Tissue Int"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Osteoporosis is characterized by an imbalance in bone remodeling, resulting in bone loss and increased fracture risk. Inflammatory diseases, such as rheumatoid arthritis, are strongly associated with secondary osteoporosis due to inflammation-induced bone loss. Pro-inflammatory cytokines, particularly TNF-\u03b1, disrupt bone homeostasis by promoting osteoclastogenesis and inhibiting osteoblast function. The Wnt signaling pathway is essential for bone formation and is suppressed in inflammatory conditions. WNT16, an osteoblast-derived ligand, increases bone mass mainly by inhibiting osteoclast differentiation but has also been found to stimulate osteoblast activity. Here we demonstrate that TNF-\u03b1 downregulates\n                    <jats:italic>Wnt16<\/jats:italic>\n                    mRNA expression in primary osteoblasts, suggesting that inflammation may impair WNT16 expression and thereby reduce bone mass. To evaluate whether pharmacological or genetical elevation of WNT16 levels can mitigate inflammation-induced bone loss, we examined the effect of WNT16 in three mouse models of local and systemic inflammation. In a knee arthritis model, intra-articular delivery of WNT16 liposomes failed to prevent local bone loss. Similarly, although osteoblast-specific WNT16 overexpression increased the overall bone mass, it did not protect against either local calvarial bone loss or systemic bone loss induced by Toll-like receptor 2 (TLR2) activation. Furthermore, in a model of systemic inflammation induced by\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , WNT16 overexpression did not preserve vertebral trabecular bone, despite increased baseline bone mass. These findings demonstrate that WNT16, although increasing the overall bone mass, is insufficient to counteract inflammation-driven bone loss.\n                  <\/jats:p>","DOI":"10.1007\/s00223-026-01481-2","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T01:49:14Z","timestamp":1769824154000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["WNT16 Overexpression is Insufficient to Counteract Inflammation-induced Bone Loss in Female Mice"],"prefix":"10.1007","volume":"117","author":[{"given":"Karin H.","family":"Nilsson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Henning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie K.","family":"Lagerquist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianyao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Bally","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulf H.","family":"Lerner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inger","family":"Gjertsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claes","family":"Ohlsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7982-7438","authenticated-orcid":false,"given":"Sofia","family":"Mov\u00e9rare-Skrtic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"1481_CR1","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1210\/endrev\/bnab028","volume":"43","author":"PR Ebeling","year":"2021","unstructured":"Ebeling PR, Nguyen HH, Aleksova J, Vincent AJ, Wong P, Milat F (2021) Secondary osteoporosis. 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