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

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

  • Bone. 2022 Apr;157:116324. doi: 10.1016/j.bone.2021.116324.
Emma Muiños Lopez 1,  Kevin Leclerc 1,  Malissa Ramsukh 1,  Paulo El Parente 1,  Karan Patel 1,  Carlos J Aranda 2,  Anna M Josephson 1,  Lindsey H Remark 3,  David J Kirby 1,  Daniel B Buchalter 1,  Tarik Hadi 4,  Sophie M Morgani 1,  Bhama Ramkhelawon 5,  Philipp Leucht 6
Affiliations

Affiliations

  • 1 Department of Orthopaedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America.
  • 2 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.
  • 3 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.
  • 4 Department of Surgery, Division of Endovascular Surgery, NYU Robert I. Grossman School of Medicine, New York, NY, United States of America.
  • 5 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.
  • 6 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.
PMID: 34998981 DOI: 10.1016/j.bone.2021.116324
Abstract

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.

Keywords

Adaptive immunity; Aging; Inflammaging; Innate immunity; Regeneration; Skeletal stem cells.

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