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

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.

SUBMITTER: Vi L

PROVIDER: S-EPMC6281653 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Vi Linda L Baht Gurpreet S GS Soderblom Erik J EJ Whetstone Heather H Wei Qingxia Q Furman Bridgette B Puviindran Vijitha V Nadesan Puviindran P Foster Matthew M Poon Raymond R White James P JP Yahara Yasuhito Y Ng Adeline A Barrientos Tomasa T Grynpas Marc M Mosely M Arthur MA Alman Benjamin A BA

Nature communications 20181205 1

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 fractu ...[more]

PMID: 30518764

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Project description:Biodegradable polycaprolactone/β-tricalcium phosphate (PT) composites are desirable candidates for bone tissue engineering applications. A higher β-tricalcium phosphate (TCP) ceramic content improves the mechanical, hydrophilic and osteogenic properties of PT scaffolds in vitro. Using a dynamic degradation reactor, we established a steady in vitro degradation model to investigate the changes in the physio-chemical and biological properties of PT scaffolds during degradation.PT46 and PT37 scaffolds underwent degradation more rapidly than PT scaffolds with lower TCP contents. In vivo studies revealed the rapid degradation of PT (PT46 and PT37) scaffolds disturbed macrophage responses and lead to bone healing failure. Macrophage co-culture assays and a subcutaneous implantation model indicated that the scaffold degradation process dynamically affected macrophage responses, especially polarization. RNA-Seq analysis indicated phagocytosis of the degradation products of PT37 scaffolds induces oxidative stress and inflammatory M1 polarization in macrophages. Overall, this study reveals that the dynamic patterns of biodegradation of degradable bone scaffolds highly orchestrate immune responses and thus determine the success of bone regeneration. Therefore, through evaluation of the biological effects of biomaterials during the entire process of degradation on immune responses and bone regeneration are necessary in order to develop more promising biomaterials for bone regeneration. Graphical abstract Schematic illustration of the mechanisms of scaffold degradation-mediated macrophage polarization and bone healing processes. A) Degradation of typical PT 55 scaffolds mediates sequential macrophage M1-M2 polarization and a matched “slow early-fast afterwards” bone regeneration mode. B) Degradation of typical PT37 scaffolds mediates ROS generation by macrophages, constant M1 polarization and a disordered “fast initially-slow in late stage” bone regeneration mode.Image 1 Highlights • This work found the vital role of bone scaffolds bio-degradation process in bone regenerative determination.• Excessive polycaprolactone/β-TCP scaffolds degradation disturbed sequential macrophages polarization.• Dynamic degradation model provided a way of investigation of degradation process of PCL/β-TCP scaffolds.• Phagocytosis of degradation products (DPs) by macrophages caused oxidative stress and M1 polarization in macrophages.

Dataset Information

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

Publications

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

Similar Datasets

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