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Early depletion of M1 macrophages retards the progression of glucocorticoid-associated osteonecrosis of the femoral head. | LitMetric

AI Article Synopsis

  • Inflammation is a key player in glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH), with M1 macrophages significantly impacting this process, although their specific roles are not well understood.
  • The study employed various methods, including RT-PCR and flow cytometry, to explore the effects of M1 macrophage-conditioned medium on mouse bone marrow-derived mesenchymal stem cells and osteocyte cultures, revealing that it induces cell apoptosis through the TNF-α mediated NF-κB signaling pathway.
  • The findings indicate that increased M1 macrophage presence correlates with GA-ONFH progression, and clearing these macrophages early on can reduce inflammatory signals, slow disease progression, and represent a

Article Abstract

Inflammation stands as a pivotal factor in the pathogenesis of glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH). However, the vital role played by M1 macrophages, the principal constituents of the inflammatory process, remains largely underexplored. In this study, we employed reverse transcription-quantitative polymerase chain Reaction (RT-PCR), western blot, and flow cytometry to assess the impact of M1-conditioned medium on cultures of mouse bone marrow-derived mesenchymal stem cells (BMSCs) and Murine Long bone Osteocyte-Y4 (MLO-Y4) in vitro. Moreover, we quantified the levels of inflammatory cytokines in the M1-conditioned medium through the employment of an enzyme-linked immunosorbent assay (ELISA). For in vivo analysis, we examined M1 macrophages and investigated the NF-kB signaling pathway in specimens obtained from the femoral heads of animals and humans. We found that the number of M1 macrophages in the femoral head of GA-ONFH patients grew significantly, and in the mice remarkably increase, maintaining high levels in the intramedullary. In vitro, the M1 macrophage-conditioned medium elicited apoptosis in BMSCs and MLO-Y4 cells, shedding light on the intricate interplay between macrophages and these cell types. The presence of TNF-α within the M1-conditioned medium activated the NF-κB pathway, providing mechanistic insight into the apoptotic induction. Moreover, employing a robust rat macrophage clearance model and GA-ONFH model, we demonstrated a remarkable attenuation in TNF-α expression and NF-kB signaling subsequent to macrophage clearance. This pronounced reduction engenders diminished cellular apoptosis and engenders a decelerated trajectory of GA-ONFH progression. In conclusion, our study reveals the crucial involvement of M1 macrophages in the pathogenesis of GA-ONFH, highlighting their indispensable role in disease progression. Furthermore, early clearance emerges as a promising strategy for impeding the development of GA-ONFH.

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Source
http://dx.doi.org/10.1016/j.intimp.2023.110639DOI Listing

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