Macrophages promote osteoblastic differentiation in-vivo: implications in fracture repair and bone homeostasis.

Published

Journal Article

Macrophages are activated in inflammation and during early phases of repair processes. Interestingly, they are also present in bone during development, but their function during this process is unclear. Here, we explore the function of macrophages in bone development, growth, and repair using transgenic mice to constitutively or conditionally deplete macrophages. Depletion of macrophages led to early skeletal growth retardation and progressive osteoporosis. By 3 months of age, macrophage-deficient mice displayed a 25% reduction in bone mineral density and a 70% reduction in the number of trabecular bone compared to control littermates. Despite depletion of macrophages, functional osteoclasts were still present in bones, lining trabecular bone and the endosteal surface of the cortical bone. Furthermore, ablation of macrophages led to a 60% reduction in the number of bone marrow mesenchymal progenitor cells and a decrease in the ability of these cells to differentiate to osteoblasts. When macrophages were depleted during fracture repair, bone union was impaired. Calluses from macrophage-deficient animals were smaller, and contained less bone and more fibrotic tissue deposition. Taken together, this shows that macrophages are crucial for maintaining bone homeostasis and promoting fracture repair by enhancing the differentiation of mesenchymal progenitors.

Full Text

Duke Authors

Cited Authors

  • Vi, L; Baht, GS; Whetstone, H; Ng, A; Wei, Q; Poon, R; Mylvaganam, S; Grynpas, M; Alman, BA

Published Date

  • June 2015

Published In

Volume / Issue

  • 30 / 6

Start / End Page

  • 1090 - 1102

PubMed ID

  • 25487241

Pubmed Central ID

  • 25487241

Electronic International Standard Serial Number (EISSN)

  • 1523-4681

Digital Object Identifier (DOI)

  • 10.1002/jbmr.2422

Language

  • eng

Conference Location

  • United States