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

dc.contributor.author

Vi, Linda

dc.contributor.author

Baht, Gurpreet S

dc.contributor.author

Soderblom, Erik J

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Whetstone, Heather

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Wei, Qingxia

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Furman, Bridgette

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Puviindran, Vijitha

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Nadesan, Puviindran

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Foster, Matthew

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Poon, Raymond

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White, James P

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Yahara, Yasuhito

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Ng, Adeline

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Barrientos, Tomasa

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Grynpas, Marc

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Mosely, M Arthur

dc.contributor.author

Alman, Benjamin A

dc.date.accessioned

2019-01-01T16:28:03Z

dc.date.available

2019-01-01T16:28:03Z

dc.date.issued

2018-12-05

dc.date.updated

2019-01-01T16:28:01Z

dc.description.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.

dc.identifier

10.1038/s41467-018-07666-0

dc.identifier.issn

2041-1723

dc.identifier.issn

2041-1723

dc.identifier.uri

https://hdl.handle.net/10161/17833

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

dc.relation.ispartof

Nature communications

dc.relation.isversionof

10.1038/s41467-018-07666-0

dc.subject

Science & Technology

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Multidisciplinary Sciences

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Science & Technology - Other Topics

dc.subject

RECEPTOR-RELATED PROTEIN-1

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NEWLY SYNTHESIZED PROTEINS

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BETA-CATENIN

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FRACTURE REPAIR

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TISSUE

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GENE

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AGE

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DIFFERENTIATION

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INACTIVATION

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REGENERATION

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Baht, Gurpreet S|0000-0002-6827-1785

duke.contributor.orcid

Foster, Matthew|0000-0003-0212-2346

pubs.begin-page

5191

pubs.issue

1

pubs.organisational-group

School of Medicine

pubs.organisational-group

Duke

pubs.organisational-group

Medicine, Pulmonary, Allergy, and Critical Care Medicine

pubs.organisational-group

Medicine

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Clinical Science Departments

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Duke Cancer Institute

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Institutes and Centers

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Cell Biology

pubs.organisational-group

Basic Science Departments

pubs.organisational-group

Orthopaedics

pubs.organisational-group

Pathology

pubs.organisational-group

Pediatrics

pubs.publication-status

Published

pubs.volume

9

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