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

Linda Vi, Gurpreet S. Baht, Erik J. Soderblom, Heather Whetstone, Qingxia Wei, Bridgette Furman, Vijitha Puviindran, Puviindran Nadesan, Matthew Foster, Raymond Poon, James P. White, Yasuhito Yahara, Adeline Ng, Tomasa Barrientos, Marc Grynpas, M. Arthur Mosely and Benjamin A. Alman ()
Additional contact information
Linda Vi: Duke University
Gurpreet S. Baht: Duke University
Erik J. Soderblom: Duke University
Heather Whetstone: University of Toronto
Qingxia Wei: University of Toronto
Bridgette Furman: Duke University
Vijitha Puviindran: Duke University
Puviindran Nadesan: Duke University
Matthew Foster: Duke University
Raymond Poon: University of Toronto
James P. White: Duke University
Yasuhito Yahara: Duke University
Adeline Ng: University of Toronto
Tomasa Barrientos: Duke University
Marc Grynpas: University of Toronto
M. Arthur Mosely: Duke University
Benjamin A. Alman: Duke University

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07666-0

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DOI: 10.1038/s41467-018-07666-0

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