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WNT16 has been suggested to play important roles in joint formation, bone homeostasis and OA development, but the mechanism of action is not clear. Transgenic mice lacking<jats:italic>Wnt16<\/jats:italic>expression (<jats:italic>Wnt16<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup>) have a more severe experimental OA than control mice. In addition,<jats:italic>Wnt16<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup>mice have a reduced cortical thickness and develop spontaneous fractures. Herein, we have used<jats:italic>Cre-Wnt16<\/jats:italic><jats:sup><jats:italic>flox\/flox<\/jats:italic><\/jats:sup>mice in which<jats:italic>Wnt16<\/jats:italic>can be conditionally ablated at any age through tamoxifen-inducible Cre-mediated recombination.<jats:italic>Wnt16<\/jats:italic>deletion was induced in 7-week-old mice to study if the<jats:italic>Cre-Wnt16<\/jats:italic><jats:sup><jats:italic>flox\/flox<\/jats:italic><\/jats:sup>mice have a more severe OA phenotype after destabilizing the medial meniscus (DMM surgery) than littermate controls with normal<jats:italic>Wnt16<\/jats:italic>expression (<jats:italic>Wnt16<\/jats:italic><jats:sup><jats:italic>flox\/flox<\/jats:italic><\/jats:sup>). WNT16 deletion was confirmed in articular cartilage and cortical bone in<jats:italic>Cre-Wnt16<\/jats:italic><jats:sup><jats:italic>flox\/flox<\/jats:italic><\/jats:sup>mice, shown by immunohistochemistry and reduced cortical bone area compared to<jats:italic>Wnt16<\/jats:italic><jats:sup><jats:italic>flox\/flox<\/jats:italic><\/jats:sup>mice. After DMM surgery, there was no difference in OA severity in the articular cartilage in the knee joint between the<jats:italic>Cre-Wnt16<\/jats:italic><jats:sup><jats:italic>flox\/flox<\/jats:italic><\/jats:sup>and<jats:italic>Wnt16<\/jats:italic><jats:sup><jats:italic>flox\/flox<\/jats:italic><\/jats:sup>mice in neither female nor male mice. In addition, there was no difference in osteophyte size in the DMM-operated tibia between the genotypes. In conclusion, inactivation of<jats:italic>Wnt16<\/jats:italic>in adult mice do not result in a more severe OA phenotype after DMM surgery. Thus, presence of WNT16 in adult mice does not have an impact on experimental OA development. Taken together, our results from<jats:italic>Cre-Wnt16<\/jats:italic><jats:sup><jats:italic>flox\/flox<\/jats:italic><\/jats:sup>mice and previous results from<jats:italic>Wnt16<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup>mice suggest that WNT16 is crucial during synovial joint establishment leading to limited joint degradation also later in life, after onset of OA. This may be important when developing new therapeutics for OA treatment.<\/jats:p>","DOI":"10.1371\/journal.pone.0277495","type":"journal-article","created":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T18:27:36Z","timestamp":1668191256000},"page":"e0277495","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Induced inactivation of Wnt16 in young adult mice has no impact on osteoarthritis development"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2621-9038","authenticated-orcid":true,"given":"Anna E.","family":"T\u00f6rnqvist","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin 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