Modulating the systemic and local adaptive immune response after fracture improves bone regeneration during aging.

Autor: Lopez EM; Department of Orthopaedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America., Leclerc K; Department of Orthopaedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America., Ramsukh M; Department of Orthopaedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America., Parente PE; Department of Orthopaedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America., Patel K; Department of Orthopaedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America., Aranda CJ; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America; Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America., Josephson AM; Department of Orthopaedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America., Remark LH; Department of Orthopaedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America; Department of Cell Biology, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America., Kirby DJ; Department of Orthopaedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America., Buchalter DB; Department of Orthopaedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America., Hadi T; Department of Surgery, Division of Endovascular Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America., Morgani SM; Department of Orthopaedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America., Ramkhelawon B; Department of Surgery, Division of Endovascular Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America; Department of Cell Biology, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America., Leucht P; Department of Orthopaedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America; Department of Cell Biology, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America. Electronic address: Philipp.leucht@nyulangone.org.
Jazyk: angličtina
Zdroj: Bone [Bone] 2022 Apr; Vol. 157, pp. 116324. Date of Electronic Publication: 2022 Jan 06.
DOI: 10.1016/j.bone.2021.116324
Abstrakt: Tissue injury leads to the well-orchestrated mobilization of systemic and local innate and adaptive immune cells. During aging, immune cell recruitment is dysregulated, resulting in an aberrant inflammatory response that is detrimental for successful healing. Here, we precisely define the systemic and local immune cell response after femur fracture in young and aging mice and identify increased toll-like receptor signaling as a potential culprit for the abnormal immune cell recruitment observed in aging animals. Myd88, an upstream regulator of TLR-signaling lies at the core of this aging phenotype, and local treatment of femur fractures with a Myd88 antagonist in middle-aged mice reverses the aging phenotype of impaired fracture healing, thus offering a promising therapeutic target that could overcome the negative impact of aging on bone regeneration.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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