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

dc.contributor.author Foster, Matthew
dc.contributor.author Alman, Benjamin
dc.contributor.author Soderblom, Erik
dc.contributor.author Vi, Linda
dc.contributor.author Baht, Gurpreet S
dc.contributor.author Whetstone, Heather
dc.contributor.author Wei, Qingxia
dc.contributor.author Furman, Bridgette
dc.contributor.author Puviindran, Vijitha
dc.contributor.author Nadesan, Puviindran
dc.contributor.author Poon, Raymond
dc.contributor.author White, James P
dc.contributor.author Yahara, Yasuhito
dc.contributor.author Ng, Adeline
dc.contributor.author Barrientos, Tomasa
dc.contributor.author Grynpas, Marc
dc.contributor.author Mosely, M Arthur
dc.date.accessioned 2019-01-01T16:28:03Z
dc.date.available 2019-01-01T16:28:03Z
dc.date.issued 2018-12-05
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.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.language eng
dc.publisher Springer Nature
dc.relation.ispartof Nature communications
dc.relation.isversionof 10.1038/s41467-018-07666-0
dc.subject Science & Technology
dc.subject Multidisciplinary Sciences
dc.subject Science & Technology - Other Topics
dc.subject RECEPTOR-RELATED PROTEIN-1
dc.subject NEWLY SYNTHESIZED PROTEINS
dc.subject BETA-CATENIN
dc.subject FRACTURE REPAIR
dc.subject TISSUE
dc.subject GENE
dc.subject AGE
dc.subject DIFFERENTIATION
dc.subject INACTIVATION
dc.subject REGENERATION
dc.title Macrophage cells secrete factors including LRP1 that orchestrate the rejuvenation of bone repair in mice.
dc.type Journal article
dc.date.updated 2019-01-01T16:28:01Z
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
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group 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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