ArticleFrontiers in bioengineering and biotechnology2022
The Dynamic Feature of Macrophage M1/M2 Imbalance Facilitates the Progression of Non-Traumatic Osteonecrosis of the Femoral Head.
Article in Frontiers in bioengineering and biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Macrophage immunometabolic reprogramming in inflammatory repair failure in osteonecrosis of the femoral head.Journal of orthopaedic translation · 2026Review
- A New Stage and Classification of Osteonecrosis of the Femoral Head Based on MRI With Pathophysiological Interpretation.Orthopaedic surgery · 2026Article
- [Effect of interleukin-33 on glucocorticoid-induced osteonecrosis of the femoral head in mice].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Article
- Kaempferol Alleviates Glucocorticoid-Induced Osteonecrosis of the Femoral Head by Modulating Macrophage M1/M2 Polarization Through RhoA/ROCK-Mediated Mitophagy Activation.Biomedicines · 2026Article
- A Hybrid Mesenchymal-Stem-Cell-Derived Decellularized Matrix Scaffold Supports Bone Repair and Vascular Perfusion in Steroid-Associated Osteonecrosis.Biomaterials research · 2026Article
- Immunomodulation in the repair of osteonecrosis of the femoral head: reprogramming strategies for macrophages and immune cells.Frontiers in immunology · 2026Review
- Inflammation in osteonecrosis of the femoral head: Evaluation of hematological biomarkers and potential prognostic value.PloS one · 2026Article
- Interactions between the gut microbiota and immune cell dynamics: novel insights into the gut-bone axis.Gut microbes · 2025Review
- Necrotic Bone Fluid Suppresses Energy Metabolism of Porcine PBMC-Derived Macrophages In Vitro.Cells · 2025Article
- Post-COVID-19 Femoral Head Osteonecrosis Exhibits Mast Cell Clusters, Fibrosis, and Vascular Thrombosis: Key Pathological Mechanisms in Long COVID-19 Bone Degeneration.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Article
- Total hip arthroplasty with tantalum rod extraction via direct anterior approach based on preoperative DCE-MRI and AI: a case report.Annals of medicine and surgery (2012) · 2025Article
- M2 macrophages-derived exosomes for osteonecrosis of femoral head treatment: modulating neutrophil extracellular traps formation and endothelial phenotype transition.Bone research · 2025Article
- The pathomechanism of bone marrow edema in the femoral head necrosis with pericollapse stage.Scientific reports · 2025Article
- Diagnostic lncRNA biomarkers and immune-related ceRNA networks for osteonecrosis of the femoral head in metabolic syndrome identified by plasma RNA sequencing and machine learning.Frontiers in immunology · 2025Article
- Immunological mechanisms in steroid-induced osteonecrosis of the femoral head.Frontiers in immunology · 2025Review
- Immunomodulatory Mechanisms of Rehmanniae Radix Praeparata-Achyranthes Root-Chinese Angelica Root Combination in Nontraumatic Osteonecrosis of the Femoral Head: A Comprehensive Network Pharmacology and Molecular Docking Study Focusing on Immunological Pathways.Mediators of inflammation · 2025Article
- Extracellular derivatives for bone metabolism.Journal of advanced research · 2024Review
- Exosomal miR-1a-3p derived from glucocorticoid-stimulated M1 macrophages promotes the adipogenic differentiation of BMSCs in glucocorticoid-associated osteonecrosis of the femoral head by targeting Cebpz.Journal of nanobiotechnology · 2024Article
- Interferon-induced factor 16 is essential in metastatic melanoma to maintain STING levels and the immune responses upon IFN-γ response pathway activation.Journal for immunotherapy of cancer · 2024Article
- Hydrogel Use in Osteonecrosis of the Femoral Head.Gels (Basel, Switzerland) · 2024Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-traumatic osteonecrosis of the femoral head (NONFH) remains a common refractory disease with poorly understood pathogenesis. Macrophage M1/M2 imbalance and chronic inflammatory microenvironment have been suggested to be closely related to osteonecrosis. Here we describe direct visual evidence for the involvement of dynamic changes in macrophages and the chronic inflammatory microenvironment in human NONFH. Osteonecrosis induces inflammatory responses and macrophage enrichment in the reparative area, and the number of inflammatory cells and macrophages falls during progressive-to end-stage NONFH. Multiplex immunohistochemistry demonstrated that macrophage M1/M2 ratio increased from 3 to 10 during progressive-to end-stage. During the progressive-stage, new blood vessels formed in the reparative area, M2 macrophages accumulated in perivascular (M1/M2 ratio ∼0.05), while M1 macrophages were enriched in avascular areas (M1/M2 ratio ∼12). Furthermore, inflammatory cytokines were detected in synovial fluid and plasma using cytometric bead arrays. Interleukin (IL)-6 and IL-1β were persistently enriched in synovial fluid compared to plasma in patients with NONFH, and this difference was confirmed by immunohistochemistry staining. However, only IL-6 levels in plasma were higher in patients with progressive-stage NONFH than in osteoarthritis. Moreover, fibrosis tissues were observed in the necrotic area in progressive-stage and end-stage NONFH based on Sirius Red staining. Together, these findings indicate that macrophage M1/M2 imbalance facilitates the progression of NONFH, a chronic inflammatory disease characterized by chronic inflammation, osteonecrosis and tissue fibrosis in the local lesion. Inhibiting inflammation, promoting the resolution of inflammation, switching macrophages to an M2 phenotype, or inhibiting their adoption of an M1 phenotype may be useful therapeutic strategies against NONFH.
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