ArticleThe Journal of biological chemistry2015
Interleukin-1 receptor-associated kinase-4 (IRAK4) promotes inflammatory osteolysis by activating osteoclasts and inhibiting formation of foreign body giant cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- ROR2 preserves alveolar bone homeostasis by orchestrating IRAK4-dependent suppression of CXCL8-driven osteolysis.Cell communication and signaling : CCS · 2026Article
- Role of the immune microenvironment in bone regeneration and progress in immune-modulating bone nanobiomaterials.Journal of Zhejiang University. Science. B · 2026Review
- Osteoporosis and Rheumatoid Arthritis: Mechanisms Underlying Osteoclast Differentiation and Activation or Factors Associated with Hip Fractures.Journal of clinical medicine · 2025Review
- IRAK4 inhibition: an effective strategy for immunomodulating peri-implant osseointegration via reciprocally-shifted polarization in the monocyte-macrophage lineage cells.BMC oral health · 2023Article
- The potential role of herbal extract Wedelolactone for treating particle-induced osteolysis: an in vivo study.Journal of orthopaedic surgery and research · 2022Article
- Effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model.Arthritis research & therapy · 2021Article
- Tooth extraction in mice administered zoledronate increases inflammatory cytokine levels and promotes osteonecrosis of the jaw.Journal of bone and mineral metabolism · 2021Article
- Learning from Monocyte-Macrophage Fusion and Multinucleation: Potential Therapeutic Targets for Osteoporosis and Rheumatoid Arthritis.International journal of molecular sciences · 2020Review
- Factors influencing multinucleated giant cell formation in vitro.Immunobiology · 2019Article
- Expression of calcification-related ion transporters during blue mussel larval development.Ecology and evolution · 2019Article
- Tumor necrosis factor receptor-associated factor 6 is required to inhibit foreign body giant cell formation and activate osteoclasts under inflammatory and infectious conditions.Journal of bone and mineral metabolism · 2018Article
- MALAT1 enhanced the proliferation of human osteoblasts treated with ultra‑high molecular weight polyethylene by targeting VEGF via miR‑22‑5p.International journal of molecular medicine · 2018Article
- Inhibition of osteolysis after local administration of osthole in a TCP particles-induced osteolysis model.International orthopaedics · 2016Article
- Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy.The Journal of biological chemistry · 2016Article
- Progranulin concentration in relation to bone mineral density among obese individuals.Archives of endocrinology and metabolismArticle
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Formation of foreign body giant cells (FBGCs) occurs following implantation of medical devices such as artificial joints and is implicated in implant failure associated with inflammation or microbial infection. Two major macrophage subpopulations, M1 and M2, play different roles in inflammation and wound healing, respectively. Therefore, M1/M2 polarization is crucial for the development of various inflammation-related diseases. Here, we show that FBGCs do not resorb bone but rather express M2 macrophage-like wound healing and inflammation-terminating molecules in vitro. We also found that FBGC formation was significantly inhibited by inflammatory cytokines or infection mimetics in vitro. Interleukin-1 receptor-associated kinase-4 (IRAK4) deficiency did not alter osteoclast formation in vitro, and IRAK4-deficient mice showed normal bone mineral density in vivo. However, IRAK4-deficient mice were protected from excessive osteoclastogenesis induced by IL-1β in vitro or by LPS, an infection mimetic of Gram-negative bacteria, in vivo. Furthermore, IRAK4 deficiency restored FBGC formation and expression of M2 macrophage markers inhibited by inflammatory cytokines in vitro or by LPS in vivo. Our results demonstrate that osteoclasts and FBGCs are reciprocally regulated and identify IRAK4 as a potential therapeutic target to inhibit stimulated osteoclastogenesis and rescue inhibited FBGC formation under inflammatory and infectious conditions without altering physiological bone resorption.
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