دورية أكاديمية
Parathyroid hormone signaling in mature osteoblasts/osteocytes protects mice from age-related bone loss.
العنوان: | Parathyroid hormone signaling in mature osteoblasts/osteocytes protects mice from age-related bone loss. |
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المؤلفون: | Uda Y; Department of Translational Dental Medicine, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA., Saini V; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Petty CA; Department of Translational Dental Medicine, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA., Alshehri M; Department of Translational Dental Medicine, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA., Shi C; Department of Translational Dental Medicine, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA.; Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, P.R. China., Spatz JM; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.; School of Medicine, University of California San Francisco, San Francisco, CA 94143, USA., Santos R; Department of Translational Dental Medicine, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA., Newell CM; Department of Translational Dental Medicine, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA., Huang TY; Department of Translational Dental Medicine, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA., Kochen A; Department of Translational Dental Medicine, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA., Kim JW; Department of Translational Dental Medicine, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA., Constantinou CK; Department of Translational Dental Medicine, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA., Saito H; Heisenberg-Group for Molecular Skeletal Biology, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany., Held KD; Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Hesse E; Heisenberg-Group for Molecular Skeletal Biology, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany., Pajevic PD; Department of Translational Dental Medicine, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA.; Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. |
المصدر: | Aging [Aging (Albany NY)] 2021 Dec 30; Vol. 13 (24), pp. 25607-25642. Date of Electronic Publication: 2021 Dec 30. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Impact Journals, LLC Country of Publication: United States NLM ID: 101508617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-4589 (Electronic) Linking ISSN: 19454589 NLM ISO Abbreviation: Aging (Albany NY) Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Albany, NY : Impact Journals, LLC |
مواضيع طبية MeSH: | Osteoblasts/*drug effects , Osteoclasts/*drug effects , Osteocytes/*drug effects , Parathyroid Hormone/*pharmacology , Receptor, Parathyroid Hormone, Type 1/*metabolism , Signal Transduction/*drug effects, Animals ; Bone Diseases, Metabolic/pathology ; Bone Resorption/metabolism ; Bone and Bones/cytology ; Bone and Bones/drug effects ; Bone and Bones/metabolism ; Homeostasis/drug effects ; Mice ; Mice, Knockout ; Osteoblasts/cytology ; Osteoblasts/metabolism ; Osteoclasts/cytology ; Osteoclasts/metabolism ; Osteocytes/metabolism ; Osteoporosis/metabolism |
مستخلص: | 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-PPR KO ) 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-PPR KO mice there was an age-dependent increase in p16 Ink4a / 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. |
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معلومات مُعتمدة: | S10 OD021652 United States OD NIH HHS; UH3 AR059655 United States AR NIAMS NIH HHS; R01 AR060221 United States AR NIAMS NIH HHS; UH2 AR059655 United States AR NIAMS NIH HHS; P30 AR066261 United States AR NIAMS NIH HHS; R56 DK079161 United States DK NIDDK NIH HHS; R01 DK079161 United States DK NIDDK NIH HHS |
فهرسة مساهمة: | Keywords: aging; osteocyte; osteoporosis; oxidative stress; parathyroid hormone |
المشرفين على المادة: | 0 (Parathyroid Hormone) 0 (Receptor, Parathyroid Hormone, Type 1) |
تواريخ الأحداث: | Date Created: 20211230 Date Completed: 20220131 Latest Revision: 20240405 |
رمز التحديث: | 20240405 |
مُعرف محوري في PubMed: | PMC8751595 |
DOI: | 10.18632/aging.203808 |
PMID: | 34968192 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1945-4589 |
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DOI: | 10.18632/aging.203808 |