M-CSF Mediates Macrophage Polarization to Regulate Chondrocyte Function in Osteoarthritis via the CSF1R/NF-κB Signaling Pathway

Bin CAO; Baojun LI; Gaisheng HE; Kang YANG; Yini MAO; Lei TANG

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Article Navigation > Journal of Kunming Medical University > 2026 > Accepted Manuscript

Bin CAO, Baojun LI, Gaisheng HE, Kang YANG, Yini MAO, Lei TANG. M-CSF Mediates Macrophage Polarization to Regulate Chondrocyte Function in Osteoarthritis via the CSF1R/NF-κB Signaling Pathway[J]. Journal of Kunming Medical University.

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M-CSF Mediates Macrophage Polarization to Regulate Chondrocyte Function in Osteoarthritis via the CSF1R/NF-κB Signaling Pathway

Department of Orthopedics，The Second People’s Hospital of Hunan Province，Changsha Hunan 410007，China

Received Date: 2026-01-16

Abstract

Abstract

Objective To investigate the effects of macrophage colony-stimulating factor （M-CSF） on chondrocyte function through macrophage polarization mediated by colony-stimulating factor 1 receptor （CSF1R） in osteoarthritis （OA）, and to elucidate the underlying mechanism. Methods Lipopolysaccharide （LPS） and interferon-gamma （IFN-γ） were used to induce mouse RAW 264.7 macrophages and primary mouse bone marrow-derived macrophages （BMDMs） to establish an OA cell model. RAW 264.7 cells were transfected with sh-NC or sh-M-CSF and treated with the CSF1R inhibitor PLX3397. Western blotting, immunofluorescence, and enzyme-linked immunosorbent assay （ELISA） were used to assess the effects of M-CSF and CSF1R on RAW 264.7 macrophage polarization. Mouse chondrocytes were co-cultured with RAW 264.7 cells or BMDMs using a Transwell co-culture system. Cell Counting Kit, Annexin V-FITC/PI apoptosis assays, ELISA, Western blotting, and immunofluorescence were used to analyze the effects of RAW 264.7 cell polarization on chondrocyte function. Results Following LPS and IFN-γ treatment , RAW 264.7 and BMDM cells underwent M1 polarization, accompanied by increased secretion of pro-inflammatory cytokines （P < 0.01） and upregulated M-CSF and CSF1R expression （P < 0.001）. Chondrocyte viability decreased （P < 0.001）, apoptosis increased （P < 0.001）, and pro-inflammatory cytokine levels rose （P < 0.001） after co-culture with induced RAW 264.7 cells or BMDMs. M-CSF knockdown or PLX3397 treatment inhibited M1 polarization （P < 0.05） and NF-κB pathway activation （P < 0.05） in RAW 264.7 cells and alleviated their damaging effects on chondrocytes （P < 0.001）. Combined M-CSF knockdown and PLX3397 treatment further inhibited M1 polarization （P < 0.01） and promoted functional recovery of chondrocytes （P < 0.001）. Conclusion M-CSF knockdown attenuates LPS- and IFN-γ-induced M1 polarization of RAW 264.7 cells by inhibiting CSF1R expression and NF-κB pathway activation, thereby alleviating chondrocyte injury.
- Osteoarthritis,
- Macrophage,
- M-CSF,
- Chondrocyte,
- CSF1R

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References(28)

References

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