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Beyond its role in the bone, Wnt is a major target for pharmaceutical inhibition in a wide range of diseases, most notably cancers. Numerous clinical trials for Wnt\u2010based candidates are currently underway, and Wnt inhibitors will likely soon be approved for clinical use. Given the bone\u2010suppressive effects accompanying Wnt inhibition, there is a need to expose alternate pathways\/molecules that can be targeted to counter the deleterious effects of Wnt inhibition on bone properties. Activation of the Pi3k\/Akt pathway via Pten deletion is one possible osteoanabolic pathway to exploit. We investigated whether the osteopenic effects of \u03b2\u2010catenin deletion from bone cells could be rescued by Pten deletion in the same cells. Mice carrying floxed alleles for Pten and \u03b2\u2010catenin were bred to Dmp1\u2010Cre mice to delete Pten alone, \u03b2\u2010catenin alone, or both genes\u00a0from the late\u2010stage osteoblast\/osteocyte population. The mice were assessed for bone mass, density, strength, and formation parameters to evaluate the potential rescue effect of Pten deletion in Wnt\u2010impaired mice. Pten deletion resulted in high bone mass and \u03b2\u2010catenin deletion resulted in low bone mass. Compound mutants had bone properties similar to \u03b2\u2010catenin mutant mice, or surprisingly in some assays, were further compromised beyond \u03b2\u2010catenin mutants. Pten inhibition, or one of its downstream nodes, is unlikely to protect against the bone\u2010wasting effects of Wnt\/\u03b2cat inhibition. Other avenues for preserving bone mass in the presence of Wnt inhibition should be explored to alleviate the skeletal side effects of Wnt inhibitor\u2010based therapies.<\/jats:p>","DOI":"10.1002\/jcp.29792","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T05:39:11Z","timestamp":1591940351000},"page":"9785-9794","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pten deletion in Dmp1\u2010expressing cells does not rescue the osteopenic effects of Wnt\/\u03b2\u2010catenin suppression"],"prefix":"10.1002","volume":"235","author":[{"given":"Kyung\u2010Eun","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Anatomy, Cell Biology &amp; Physiology Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"April M.","family":"Hoggatt","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology &amp; Physiology Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Whitney A.","family":"Bullock","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology &amp; Physiology Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Horan","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology &amp; Physiology Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Yokota","sequence":"additional","affiliation":[{"name":"Indiana Center for Musculoskeletal Health Indianapolis Indiana"},{"name":"Department of Biomedical Engineering Indiana University\u2013Purdue University at Indianapolis Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick M.","family":"Pavalko","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology &amp; Physiology Indiana University School of Medicine Indianapolis Indiana"},{"name":"Indiana Center for Musculoskeletal Health Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3989-4780","authenticated-orcid":false,"given":"Alexander G.","family":"Robling","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology &amp; Physiology Indiana University School of Medicine Indianapolis Indiana"},{"name":"Indiana Center for Musculoskeletal Health Indianapolis Indiana"},{"name":"Department of Biomedical Engineering Indiana University\u2013Purdue University at Indianapolis Indianapolis Indiana"},{"name":"Richard L. 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