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Macrophage cells secrete factors including LRP1 that orchestrate the rejuvenation of bone repair in mice.
Vi, Linda; Baht, Gurpreet S; Soderblom, Erik J; Whetstone, Heather; Wei, Qingxia; Furman, Bridgette; Puviindran, Vijitha; Nadesan, Puviindran; Foster, Matthew; Poon, Raymond; White, James P; Yahara, Yasuhito; Ng, Adeline; Barrientos, Tomasa; Grynpas, Marc; Mosely, M Arthur; Alman, Benjamin A.
Afiliación
  • Vi L; Department of Orthopaedic Surgery, Duke University, Durham, 27710, USA.
  • Baht GS; Hospital for Sick Children, University of Toronto, Toronto, M5G1X8, Canada.
  • Soderblom EJ; Division of Physical Medicine and Rehabilitation, University of Toronto, M5G 2C4, USA.
  • Whetstone H; Department of Orthopaedic Surgery, Duke University, Durham, 27710, USA.
  • Wei Q; Duke Molecular Physiology Institute, Duke University, Durham, 27701, USA.
  • Furman B; Proteomics and Metabolomics Shared Resource, Duke University, Durham, 27701, USA.
  • Puviindran V; Hospital for Sick Children, University of Toronto, Toronto, M5G1X8, Canada.
  • Nadesan P; Hospital for Sick Children, University of Toronto, Toronto, M5G1X8, Canada.
  • Foster M; Department of Orthopaedic Surgery, Duke University, Durham, 27710, USA.
  • Poon R; Department of Orthopaedic Surgery, Duke University, Durham, 27710, USA.
  • White JP; Department of Orthopaedic Surgery, Duke University, Durham, 27710, USA.
  • Yahara Y; Proteomics and Metabolomics Shared Resource, Duke University, Durham, 27701, USA.
  • Ng A; Hospital for Sick Children, University of Toronto, Toronto, M5G1X8, Canada.
  • Barrientos T; Duke Molecular Physiology Institute, Duke University, Durham, 27701, USA.
  • Grynpas M; Department of Orthopaedic Surgery, Duke University, Durham, 27710, USA.
  • Mosely MA; Mount Sinai Hospital, University of Toronto, Toronto, M5G1X5, Canada.
  • Alman BA; Department of Orthopaedic Surgery, Duke University, Durham, 27710, USA.
Nat Commun ; 9(1): 5191, 2018 12 05.
Article en En | MEDLINE | ID: mdl-30518764
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de LDL / Curación de Fractura / Proteínas Supresoras de Tumor / Fracturas Óseas / Macrófagos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de LDL / Curación de Fractura / Proteínas Supresoras de Tumor / Fracturas Óseas / Macrófagos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido