Monocyte/Macrophage Lineage Cells From Fetal Erythromyeloid Progenitors Orchestrate Bone Remodeling and Repair
Open Access
- 4 February 2021
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Cell and Developmental Biology
Abstract
A third of the population sustains a bone fracture, and the pace of fracture healing slows with age. The slower pace of repair is responsible for the increased morbidity in older individuals who sustain a fracture. Bone healing progresses through overlapping phases, initiated by cells of the monocyte/macrophage lineage. The repair process ends with remodeling. This last phase is controlled by osteoclasts, which are bone-specific multinucleated cells also of the monocyte/macrophage lineage. The slower rate of healing in aging can be rejuvenated by macrophages from young animals, and secreted proteins from macrophage regulate undifferentiated mesenchymal cells to become bone-forming osteoblasts. Macrophages can derive from fetal erythromyeloid progenitors or from adult hematopoietic progenitors. Recent studies show that fetal erythromyeloid progenitors are responsible for the osteoclasts that form the space in bone for hematopoiesis and the fetal osteoclast precursors reside in the spleen postnatally, traveling through the blood to participate in fracture repair. Differences in secreted proteins between macrophages from old and young animals regulate the efficiency of osteoblast differentiation from undifferentiated mesenchymal precursor cells. Interestingly, during the remodeling phase osteoclasts can form from the fusion between monocyte/macrophage lineage cells from the fetal and postnatal precursor populations. Data from single cell RNA sequencing identifies specific markers for populations derived from the different precursor populations, a finding that can be used in future studies. Here, we review the diversity of macrophages and osteoclasts, and discuss recent finding about their developmental origin and functions, which provides novel insights into their roles in bone homeostasis and repair.Keywords
Funding Information
- National Institute on Aging
This publication has 213 references indexed in Scilit:
- Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op miceProceedings of the National Academy of Sciences of the United States of America, 2012
- Osteoclast Fusion and FissionCalcified Tissue International, 2012
- Human Early Fracture Hematoma Is Characterized by Inflammation and HypoxiaClinical Orthopaedics and Related Research, 2011
- Hematopoietic stem cell: self‐renewal versus differentiationWires Systems Biology and Medicine, 2010
- Circulating mitochondrial DAMPs cause inflammatory responses to injuryNature, 2010
- Expression of AA4.1 marks lymphohematopoietic progenitors in early mouse developmentProceedings of the National Academy of Sciences of the United States of America, 2009
- Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasisNature, 2009
- Exploring the full spectrum of macrophage activationNature Reviews Immunology, 2008
- Of lineage and legacy: the development of mammalian hematopoietic stem cellsNature Immunology, 2008
- Osteoclast differentiation and activationNature, 2003