| Title: | Postnatal deletion of beta-catenin in osterix-expressing cells is necessary for bone growth and intermittent PTH-induced bone gain |
| Author(s): | Yu C; Xuan M; Zhang M; Yao Q; Zhang K; Zhang X; Guo J; Song L; |
| Address: | "Department of Endocrinology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Rd, Shanghai, 200065, China. Department of Orthopaedics, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China. Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. Department of Endocrinology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Rd, Shanghai, 200065, China. 6songlige@tongji.edu.cn" |
| DOI: | 10.1007/s00774-017-0873-0 |
| ISSN/ISBN: | 1435-5604 (Electronic) 0914-8779 (Linking) |
| Abstract: | "wnt/beta-catenin signaling has been shown to influence bone homeostasis and is important for parathyroid hormone (PTH)-induced bone gain. To further understand the role of beta-catenin in the early stages of osteoblastic lineage cells for postnatal bone homeostasis and the anabolic actions of PTH on bone, we examined mice with postnatal disruption of beta-catenin in osterix-expressing cells (beta-catenin KO mice) by mating floxed beta-catenin mice with transgenic mice expressing cre under the control of the osterix promoter suppressible by doxycycline. After withdrawal of doxycycline, beta-catenin KO mice developed progressive bone loss, ectopic cartilage formation, accumulation of mesenchymal stromal cells, and bone marrow adiposity. The beta-catenin-defective osteoblasts sorted by flow cytometry from beta-catenin KO mice exhibited decreased EdU incorporation, increased annexin V activity, and profound alterations in gene expression including wnt target genes, osteoclast regulators, and osteoblast markers. A dramatic increase in osteoclasts was observed in both neonatal and postnatal beta-catenin KO mice. Intermittent administration of PTH for 4 weeks significantly increased bone mass in control mice; however, this anabolic effect of PTH was substantially blunted in beta-catenin KO mice. Our data indicate that beta-catenin in osterix-expressing cells is required for postnatal osteoblast differentiation, osteoblast proliferation, and bone resorption, and is essential for the anabolic actions of PTH in bone" |
| Keywords: | "Adiposity/drug effects Anabolic Agents/pharmacology Animals Animals, Newborn Apoptosis/drug effects Bone Development/*drug effects Bone Marrow/drug effects/metabolism Bone Resorption/metabolism/pathology Bone and Bones/*metabolism Cartilage/drug effects/m;" |
| Notes: | "MedlineYu, Caixia Xuan, Miao Zhang, Mingzhu Yao, Qianqian Zhang, Keqin Zhang, Xiuzhen Guo, Jun Song, Lige eng PO1 DK11794/National Institutes of Health/ 81300712/National Natural Science Foundation of China/ 81401782/National Natural Science Foundation of China/ 13ZR1438000/Shanghai Science and Technology Foundation/ 20130072120014/Research Fund for the Doctoral Program of Higher Education of China/ Japan 2017/11/11 J Bone Miner Metab. 2018 Sep; 36(5):560-572. doi: 10.1007/s00774-017-0873-0. Epub 2017 Nov 9" |
