Parathyroid hormone signaling in mature osteoblasts/osteocytes protects mice from age-related bone loss
| Autor: | Yuhei Uda, Vaibhav Saini, Christopher A. Petty, Majed Alshehri, Chao Shi, Jordan M. Spatz, Roberto Santos, Carly M. Newell, Tim Y. Huang, Alejandro Kochen, Ji W. Kim, Christodoulos K. Constantinou, Hiroaki Saito, Kathryn D. Held, Eric Hesse, Paola Divieti Pajevic |
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| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
Mice Knockout Osteoblasts osteocyte aging Osteoclasts Cell Biology Osteocytes osteoporosis Bone and Bones Bone Diseases Metabolic Mice Parathyroid Hormone Animals Homeostasis oxidative stress Bone Resorption Receptor Parathyroid Hormone Type 1 Signal Transduction Priority Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Aging is accompanied by osteopenia, characterized by reduced bone formation and increased bone resorption. Osteocytes, the terminally differentiated osteoblasts, are regulators of bone homeostasis, and parathyroid hormone (PTH) receptor (PPR) signaling in mature osteoblasts/osteocytes is essential for PTH-driven anabolic and catabolic skeletal responses. However, the role of PPR signaling in those cells during aging has not been investigated. The aim of this study was to analyze the role of PTH signaling in mature osteoblasts/osteocytes during aging. Mice lacking PPR in osteocyte (Dmp1-PPRKO) display an age-dependent osteopenia characterized by a significant decrease in osteoblast activity and increase in osteoclast number and activity. At the molecular level, the absence of PPR signaling in mature osteoblasts/osteocytes is associated with an increase in serum sclerostin and a significant increase in osteocytes expressing 4-hydroxy-2-nonenals, a marker of oxidative stress. In Dmp1-PPRKO mice there was an age-dependent increase in p16Ink4a/Cdkn2a expression, whereas it was unchanged in controls. In vitro studies demonstrated that PTH protects osteocytes from oxidative stress-induced cell death. In summary, we reported that PPR signaling in osteocytes is important for protecting the skeleton from age-induced bone loss by restraining osteoclast’s activity and protecting osteocytes from oxidative stresses. |
| Databáze: | OpenAIRE |
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