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

Emma Muiños Lopez; Kevin Leclerc; Malissa Ramsukh; Paulo EL Parente; Karan Patel; Carlos J. Aranda; Anna M. Josephson; Lindsey H. Remark; David J. Kirby; Daniel B. Buchalter; Tarik Hadi; Sophie M. Morgani; Bhama Ramkhelawon; Philipp Leucht

doi:10.1016/j.bone.2021.116324

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

Emma Muiños Lopez, Kevin Leclerc, Malissa Ramsukh, Paulo EL Parente, Karan Patel, Carlos J. Aranda, Anna M. Josephson, Lindsey H. Remark, David J. Kirby, Daniel B. Buchalter, Tarik Hadi, Sophie M. Morgani, Bhama Ramkhelawon, Philipp Leucht

Icahn School of Medicine at Mount Sinai

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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.

Original language	English
Article number	116324
Journal	Bone
Volume	157
DOIs	https://doi.org/10.1016/j.bone.2021.116324
State	Published - Apr 2022

Keywords

Adaptive immunity
Aging
Inflammaging
Innate immunity
Regeneration
Skeletal stem cells

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Lopez, E. M., Leclerc, K., Ramsukh, M., Parente, P. EL., Patel, K., Aranda, C. J., Josephson, A. M., Remark, L. H., Kirby, D. J., Buchalter, D. B., Hadi, T., Morgani, S. M., Ramkhelawon, B., & Leucht, P. (2022). Modulating the systemic and local adaptive immune response after fracture improves bone regeneration during aging. Bone, 157, Article 116324. https://doi.org/10.1016/j.bone.2021.116324

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title = "Modulating the systemic and local adaptive immune response after fracture improves bone regeneration during aging",

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",

author = "Lopez, {Emma Mui{\~n}os} and Kevin Leclerc and Malissa Ramsukh and Parente, {Paulo EL} and Karan Patel and Aranda, {Carlos J.} and Josephson, {Anna M.} and Remark, {Lindsey H.} and Kirby, {David J.} and Buchalter, {Daniel B.} and Tarik Hadi and Morgani, {Sophie M.} and Bhama Ramkhelawon and Philipp Leucht",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2022",

month = apr,

doi = "10.1016/j.bone.2021.116324",

language = "English",

volume = "157",

journal = "Bone",

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T1 - Modulating the systemic and local adaptive immune response after fracture improves bone regeneration during aging

AU - Lopez, Emma Muiños

AU - Leclerc, Kevin

AU - Ramsukh, Malissa

AU - Parente, Paulo EL

AU - Patel, Karan

AU - Aranda, Carlos J.

AU - Josephson, Anna M.

AU - Remark, Lindsey H.

AU - Kirby, David J.

AU - Buchalter, Daniel B.

AU - Hadi, Tarik

AU - Morgani, Sophie M.

AU - Ramkhelawon, Bhama

AU - Leucht, Philipp

PY - 2022/4

Y1 - 2022/4

N2 - 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.

AB - 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.

KW - Adaptive immunity

KW - Aging

KW - Inflammaging

KW - Innate immunity

KW - Regeneration

KW - Skeletal stem cells

UR - http://www.scopus.com/inward/record.url?scp=85122641856&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2021.116324

DO - 10.1016/j.bone.2021.116324

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AN - SCOPUS:85122641856

SN - 8756-3282

VL - 157

JO - Bone

JF - Bone

M1 - 116324

ER -

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

Abstract

Keywords

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