دورية أكاديمية
أعرض في EDS

Osteocyte RANKL is required for cortical bone loss with age and is induced by senescence.

التفاصيل البيبلوغرافية
العنوان: Osteocyte RANKL is required for cortical bone loss with age and is induced by senescence.
المؤلفون: Kim HN; Center for Musculoskeletal Disease Research.; Division of Endocrinology, Department of Internal Medicine, and., Xiong J; Center for Musculoskeletal Disease Research.; Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA., MacLeod RS; Center for Musculoskeletal Disease Research.; Division of Endocrinology, Department of Internal Medicine, and., Iyer S; Center for Musculoskeletal Disease Research.; Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA., Fujiwara Y; Center for Musculoskeletal Disease Research.; Division of Endocrinology, Department of Internal Medicine, and., Cawley KM; Center for Musculoskeletal Disease Research.; Division of Endocrinology, Department of Internal Medicine, and., Han L; Division of Endocrinology, Department of Internal Medicine, and., He Y; Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida, USA., Thostenson JD; Center for Musculoskeletal Disease Research.; Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA., Ferreira E; Center for Musculoskeletal Disease Research.; Division of Endocrinology, Department of Internal Medicine, and., Jilka RL; Center for Musculoskeletal Disease Research.; Division of Endocrinology, Department of Internal Medicine, and., Zhou D; Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida, USA., Almeida M; Center for Musculoskeletal Disease Research.; Division of Endocrinology, Department of Internal Medicine, and.; Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA., O'Brien CA; Center for Musculoskeletal Disease Research.; Division of Endocrinology, Department of Internal Medicine, and.; Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.; Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA.
المصدر: JCI insight [JCI Insight] 2020 Oct 02; Vol. 5 (19). Date of Electronic Publication: 2020 Oct 02.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]-
مواضيع طبية MeSH: Cellular Senescence*, Aging/*pathology , Bone Resorption/*pathology , Cortical Bone/*pathology , Osteocytes/*pathology , RANK Ligand/*physiology, Aging/metabolism ; Animals ; Bone Resorption/etiology ; Bone Resorption/metabolism ; Cortical Bone/metabolism ; Female ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Osteocytes/metabolism
مستخلص: In aging mice, osteoclast number increases in cortical bone but declines in trabecular bone, suggesting that different mechanisms underlie age-associated bone loss in these 2 compartments. Osteocytes produce the osteoclastogenic cytokine RANKL, encoded by Tnfsf11. Tnfsf11 mRNA increases in cortical bone of aged mice, suggesting a mechanism underlying the bone loss. To address this possibility, we aged mice lacking RANKL in osteocytes. Whereas control mice lost cortical bone between 8 and 24 months of age, mice lacking RANKL in osteocytes gained cortical bone during this period. Mice of both genotypes lost trabecular bone with age. Osteoclasts increased with age in cortical bone of control mice but not in RANKL conditional knockout mice. Induction of cellular senescence increased RANKL production in murine and human cell culture models, suggesting an explanation for elevated RANKL levels with age. Overexpression of the senescence-associated transcription factor Gata4 stimulated Tnfsf11 expression in cultured murine osteoblastic cells. Finally, elimination of senescent cells from aged mice using senolytic compounds reduced Tnfsf11 mRNA in cortical bone. Our results demonstrate the requirement of osteocyte-derived RANKL for age-associated cortical bone loss and suggest that increased Tnfsf11 expression with age results from accumulation of senescent cells in cortical bone.
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معلومات مُعتمدة: P20 GM125503 United States GM NIGMS NIH HHS; R01 AR049794 United States AR NIAMS NIH HHS; R01 AR056679 United States AR NIAMS NIH HHS; UL1 TR003107 United States TR NCATS NIH HHS; R01 AG063801 United States AG NIA NIH HHS; I01 BX000294 United States BX BLRD VA; M01 RR000080 United States RR NCRR NIH HHS
فهرسة مساهمة: Keywords: Bone Biology; Bone disease
المشرفين على المادة: 0 (RANK Ligand)
0 (Tnfsf11 protein, mouse)
تواريخ الأحداث: Date Created: 20200902 Date Completed: 20210609 Latest Revision: 20210609
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7566701
DOI: 10.1172/jci.insight.138815
PMID: 32870816
قاعدة البيانات: MEDLINE
الوصف
تدمد:2379-3708
DOI:10.1172/jci.insight.138815