| First Author | Lim KE | Year | 2020 |
| Journal | J Cell Physiol | Volume | 235 |
| Issue | 12 | Pages | 9785-9794 |
| PubMed ID | 32529635 | Mgi Jnum | J:330754 |
| Mgi Id | MGI:6714581 | Doi | 10.1002/jcp.29792 |
| Citation | Lim KE, et al. (2020) Pten deletion in Dmp1-expressing cells does not rescue the osteopenic effects of Wnt/beta-catenin suppression. J Cell Physiol 235(12):9785-9794 |
| abstractText | Skeletal homeostasis is sensitive to perturbations in Wnt signaling. 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-based candidates are currently underway, and Wnt inhibitors will likely soon be approved for clinical use. Given the bone-suppressive 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 beta-catenin deletion from bone cells could be rescued by Pten deletion in the same cells. Mice carrying floxed alleles for Pten and beta-catenin were bred to Dmp1-Cre mice to delete Pten alone, beta-catenin alone, or both genes from the late-stage 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-impaired mice. Pten deletion resulted in high bone mass and beta-catenin deletion resulted in low bone mass. Compound mutants had bone properties similar to beta-catenin mutant mice, or surprisingly in some assays, were further compromised beyond beta-catenin mutants. Pten inhibition, or one of its downstream nodes, is unlikely to protect against the bone-wasting effects of Wnt/betacat 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-based therapies. |
