| First Author | Kedlaya R | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 8 | Pages | 3047-57 |
| PubMed ID | 27253995 | Mgi Jnum | J:239764 |
| Mgi Id | MGI:5829616 | Doi | 10.1210/en.2015-1587 |
| Citation | Kedlaya R, et al. (2016) Adult-Onset Deletion of beta-Catenin in (10kb)Dmp1-Expressing Cells Prevents Intermittent PTH-Induced Bone Gain. Endocrinology 157(8):3047-57 |
| abstractText | beta-Catenin (betacat) is a major downstream signaling node in canonical Wingless-related integration site (Wnt) signaling pathway, and its activity is crucial for canonical Wnt signal transduction. Wnt signaling has recently been implicated in the osteo-anabolic response to PTH, a potent calcium-regulating factor. We investigated whether betacat is essential for the anabolic action of intermittent PTH by generating male mice with adult-onset deletion of betacat in a subpopulation of bone cells (osteocytes and late-stage osteoblasts), treating them with an anabolic regimen of PTH, and measuring the skeletal responses. Male (10kb)Dmp1-CreERt2 transgenic mice that also harbored floxed loss-of-function betacat alleles (betacat(f/f)) were induced for Cre activity using tamoxifen, then injected daily with human PTH 1-34 (30 mug/kg) or vehicle for 5 weeks. Mice in which betacat was deleted showed either total lack of bone mineral density (BMD) gain, or BMD loss, and did not respond to PTH treatment. However, bone mass measurements in the trabecular compartment of the femur and spine revealed PTH-induced bone gain whether betacat was deleted or not. PTH-stimulated increases in periosteal and cancellous bone formation rates were not impaired by betacat deletion, but resorption markers and cortical porosity were significantly increased in induced mice, particularly induced mice treated with PTH. These results suggest that betacat is required for net-positive BMD effects of PTH therapy but that the anabolic effects per se of PTH treatment might not require osteocytic/osteoblastic betacat. |
