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Nat Commun. 2018 Dec 5;9(1):5191. doi: 10.1038/s41467-018-07666-0.

Macrophage cells secrete factors including LRP1 that orchestrate the rejuvenation of bone repair in mice.

Author information

1
Department of Orthopaedic Surgery, Duke University, Durham, 27710, USA.
2
Hospital for Sick Children, University of Toronto, Toronto, M5G1X8, Canada.
3
Division of Physical Medicine and Rehabilitation, University of Toronto, M5G 2C4, USA.
4
Duke Molecular Physiology Institute, Duke University, Durham, 27701, USA.
5
Proteomics and Metabolomics Shared Resource, Duke University, Durham, 27701, USA.
6
Mount Sinai Hospital, University of Toronto, Toronto, M5G1X5, Canada.
7
Department of Orthopaedic Surgery, Duke University, Durham, 27710, USA. ben.alman@duke.edu.
8
Regeneration Next, Duke University, Durham, 27710, USA. ben.alman@duke.edu.

Abstract

The pace of repair declines with age and, while exposure to a young circulation can rejuvenate fracture repair, the cell types and factors responsible for rejuvenation are unknown. Here we report that young macrophage cells produce factors that promote osteoblast differentiation of old bone marrow stromal cells. Heterochronic parabiosis exploiting young mice in which macrophages can be depleted and fractionated bone marrow transplantation experiments show that young macrophages rejuvenate fracture repair, and old macrophage cells slow healing in young mice. Proteomic analysis of the secretomes identify differential proteins secreted between old and young macrophages, such as low-density lipoprotein receptor-related protein 1 (Lrp1). Lrp1 is produced by young cells, and depleting Lrp1 abrogates the ability to rejuvenate fracture repair, while treating old mice with recombinant Lrp1 improves fracture healing. Macrophages and proteins they secrete orchestrate the fracture repair process, and young cells produce proteins that rejuvenate fracture repair in mice.

PMID:
30518764
PMCID:
PMC6281653
DOI:
10.1038/s41467-018-07666-0
[Indexed for MEDLINE]
Free PMC Article

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