The macrophage’s role on bone remodeling and osteogenesis: a systematic review

João Maria Orvalho, Juliana Campos Hasse Fernandes, Rogerio Moraes Castilho, Gustavo Vicentis Oliveira Fernandes*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)


Macrophages are one of the most abundant immune cells in the human body. They have several roles and functions in the body; however, their role in bone osteogenesis and remodulation has yet to be accurately determined. Thus, this systematic review aimed to determine and explain the macrophages’ role associated with remodeling and osteogenesis. Electronic search was conducted through MEDLINE (PubMed) and Web of Science (WoS), with the following focused question “What is the real macrophages’ role in the bone remodeling and osteogenesis and what would be the conditions to trigger the behavior?” After initial screening of 7051 articles, 31 were remained for full-text reading. Then, after revision and evaluation, 25 articles were included for the final qualitative analysis. Macrophages can be divided into inflammatory M1 macrophages and anti-inflammatory M2 macrophages. M1 and M2 act in a fracture and release proinflammatory cytokines recruiting cells, such as mesenchymal stem cells (MSCs), and increase osteoclast activity. After a few days, the inflammatory process stops, and M1 macrophages differentiate to M2 macrophages in the presence of IL-4. M2 macrophages release anti-inflammatory cytokines, upregulating RUNX-2 in MSCs, who consequently are differentiated to osteoblasts. These cells will produce bone matrix (osteocalcin, osteopontin, and collagen I), building/repairing the area. Based on the information gathered, it was possible to conclude that macrophages have a crucial role within osteogenesis, and both M1 and M2 macrophages are essential to make the inflammatory and remodeling phase have an adequate formation/recovery. Graphical Abstract: Summarization of all findings related to this systematic review, reporting the phases, involvement, and behavior of macrophages and other constituents.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalClinical Reviews in Bone and Mineral Metabolism
Issue number1-4
Publication statusPublished - Dec 2023


  • Bone remodeling
  • Bone repair
  • Macrophages
  • Osteogenesis


Dive into the research topics of 'The macrophage’s role on bone remodeling and osteogenesis: a systematic review'. Together they form a unique fingerprint.

Cite this