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. |
| References: | Front Immunol. 2019 Dec 13;10:2925. (PMID: 31921183) Am J Physiol Endocrinol Metab. 2006 Jul;291(1):E38-49. (PMID: 16449303) Science. 1991 Nov 15;254(5034):1024-6. (PMID: 1658941) EMBO J. 2003 Dec 1;22(23):6267-76. (PMID: 14633986) J Biol Chem. 2014 Jun 13;289(24):16699-710. (PMID: 24753250) Horm Mol Biol Clin Investig. 2016 Oct 1;28(1):21-38. (PMID: 27149203) FASEB J. 2020 Aug;34(8):10191-10211. (PMID: 32557809) J Bone Miner Res. 2017 Mar;32(3):522-535. (PMID: 27704638) Bone. 2002 Jul;31(1):57-61. (PMID: 12110413) Cell Metab. 2007 Jun;5(6):464-75. (PMID: 17550781) Int J Biol Sci. 2018 Apr 5;14(5):508-517. (PMID: 29805302) N Engl J Med. 1994 Dec 15;331(24):1618-23. (PMID: 7969342) JBMR Plus. 2021 Dec 10;6(2):e10579. (PMID: 35229061) Nature. 2003 Oct 23;425(6960):841-6. (PMID: 14574413) Methods Mol Biol. 2007;371:179-89. (PMID: 17634582) Nat Med. 2011 Sep 11;17(10):1235-41. (PMID: 21909103) J Biol Chem. 2015 Jul 3;290(27):16744-58. (PMID: 25953900) J Immunol. 2010 Aug 15;185(4):2570-9. (PMID: 20644167) Pharmacogenomics. 2012 May;13(7):815-29. (PMID: 22594513) Acta Orthop. 2011 Oct;82(5):628-32. (PMID: 22103277) Nat Med. 2017 Sep;23(9):1072-1079. (PMID: 28825716) PLoS One. 2008 Aug 13;3(8):e2942. (PMID: 18698360) Biomark Res. 2017 May 18;5:18. (PMID: 28529755) J Mol Endocrinol. 2019 Feb 1;62(2):R167-R185. (PMID: 30532996) Cell Rep. 2018 Feb 6;22(6):1531-1544. (PMID: 29425508) J Biol Chem. 2013 Jul 12;288(28):20122-34. (PMID: 23729679) Free Radic Biol Med. 2007 Jun 15;42(12):1858-65. (PMID: 17512465) Blood. 2013 Feb 7;121(6):930-9. (PMID: 23160461) FASEB J. 2018 Jan;32(1):440-452. (PMID: 28928248) J Bone Miner Res. 2015 Nov;30(11):1969-79. (PMID: 25917430) Diabetes. 2015 Dec;64(12):4075-87. (PMID: 26340931) J Bone Miner Res. 2011 Feb;26(2):229-38. (PMID: 21254230) Clin Genet. 2003 Mar;63(3):192-7. (PMID: 12694228) Nat Med. 2011 Sep 11;17(10):1231-4. (PMID: 21909105) J Cell Physiol. 2017 Apr;232(4):785-796. (PMID: 27357344) J Bone Miner Res. 2015 Mar;30(3):400-11. (PMID: 25271055) Nat Commun. 2016 Oct 19;7:13176. (PMID: 27759007) Arch Biochem Biophys. 2008 May 15;473(2):106-11. (PMID: 18424256) Int J Biochem Cell Biol. 2004 Jan;36(1):1-8. (PMID: 14592527) Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20309-14. (PMID: 19091948) J Clin Invest. 1999 Aug;104(4):439-46. (PMID: 10449436) Cell Metab. 2017 Mar 7;25(3):661-672. (PMID: 28162969) Aging Cell. 2010 Oct;9(5):851-67. (PMID: 20698835) JCI Insight. 2020 Oct 2;5(19):. (PMID: 32870816) J Bone Miner Res. 2012 May;27(5):1018-29. (PMID: 22308018) Exp Gerontol. 2006 Nov;41(11):1080-93. (PMID: 17092679) Nat Rev Nephrol. 2013 Nov;9(11):641-9. (PMID: 23877588) Bone. 2005 Aug;37(2):148-58. (PMID: 15946907) J Bone Miner Res. 1998 May;13(5):793-802. (PMID: 9610743) Bone. 2009 Sep;45(3):590-602. (PMID: 19450716) Biochem Biophys Res Commun. 2007 Oct 26;362(3):550-3. (PMID: 17719560) Nat Biotechnol. 2007 Feb;25(2):238-43. (PMID: 17237769) Cell Stem Cell. 2013 Jun 6;12(6):737-47. (PMID: 23746979) |
| 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 |