دورية أكاديمية

Adult-Onset Deletion of β-Catenin in 10kbDmp1-Expressing Cells Prevents Intermittent PTH-Induced Bone Gain

التفاصيل البيبلوغرافية
العنوان: Adult-Onset Deletion of β-Catenin in 10kbDmp1-Expressing Cells Prevents Intermittent PTH-Induced Bone Gain
المؤلفون: Kedlaya, Rajendra, Kang, Kyung Shin, Hong, Jung Min, Bettagere, Vidya, Lim, Kyung-Eun, Horan, Daniel, Divieti-Pajevic, Paola, Robling, Alexander G.
المساهمون: Anatomy and Cell Biology, School of Medicine
المصدر: PMC
بيانات النشر: Oxford Academic
سنة النشر: 2016
المجموعة: Indiana University - Purdue University Indianapolis: IUPUI Scholar Works
مصطلحات موضوعية: Bone Gain, β-Catenin (βcat), calcium-regulating factor
الوصف: β-Catenin (βcat) 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 βcat is essential for the anabolic action of intermittent PTH by generating male mice with adult-onset deletion of βcat 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 10kbDmp1-CreERt2 transgenic mice that also harbored floxed loss-of-function βcat alleles (βcatf/f) were induced for Cre activity using tamoxifen, then injected daily with human PTH 1–34 (30 μg/kg) or vehicle for 5 weeks. Mice in which βcat 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 βcat was deleted or not. PTH-stimulated increases in periosteal and cancellous bone formation rates were not impaired by βcat deletion, but resorption markers and cortical porosity were significantly increased in induced mice, particularly induced mice treated with PTH. These results suggest that βcat 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 βcat.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
تدمد: 0013-7227
العلاقة: Endocrinology; Kedlaya, R., Kang, K. S., Hong, J. M., Bettagere, V., Lim, K.-E., Horan, D., … Robling, A. G. (2016). Adult-Onset Deletion of β-Catenin in 10kbDmp1-Expressing Cells Prevents Intermittent PTH-Induced Bone Gain. Endocrinology, 157(8), 3047–3057. https://doi.org/10.1210/en.2015-1587Test; https://hdl.handle.net/1805/15293Test
الإتاحة: https://doi.org/10.1210/en.2015-1587Test
https://hdl.handle.net/1805/15293Test
حقوق: Publisher Policy
رقم الانضمام: edsbas.4BE1F115
قاعدة البيانات: BASE