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

doi:10.12259/j.issn.2095-610X.S20261005

Volume 47 Issue 10

Oct. 2026

Turn off MathJax

Article Contents

Article Navigation > Journal of Kunming Medical University > 2026 > 47(10): 55-67

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, 2026, 47(10): 55-67. doi: 10.12259/j.issn.2095-610X.S20261005

Citation:

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, 2026, 47(10): 55-67. doi: 10.12259/j.issn.2095-610X.S20261005

Citation:

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, 2026, 47(10): 55-67. doi: 10.12259/j.issn.2095-610X.S20261005

PDF( 19350 KB)

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

doi: 10.12259/j.issn.2095-610X.S20261005

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

Received Date: 2026-01-16
Available Online: 2026-09-25
Publish Date: 2026-10-30

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

FullText(HTML)

References(28)

References

[1]	Zhang Y, Han Y, Sun Y, et al. Osteoarthritis: Molecular pathogenesis and potential therapeutic options[J]. Signal Transduct Target Ther, 2026, 11: 81. doi: 10.1038/s41392-025-02556-6
[2]	Hao T, Pei Z, Hu S, et al. Identification of osteoarthritis-associated chondrocyte subpopulations and key gene-regulating drugs based on multi-omics analysis[J]. Sci Rep, 2025, 15: 12448. doi: 10.1038/s41598-025-90694-w
[3]	Mei Z, Yilamu K, Ni W, et al. Chondrocyte fatty acid oxidation drives osteoarthritis via SOX9 degradation and epigenetic regulation[J]. Nat Commun, 2025, 16(1): 4892. doi: 10.1038/s41467-025-60037-4
[4]	Li Y, Li H, Chen X, et al. CDK5 regulates PPARγ/NF-κB signaling to exacerbate obesity-related osteoarthritis via modulating macrophage polarization and chondrocyte apoptosis[J]. Cell Mol Biol Lett, 2025, 30(1): 135. doi: 10.1186/s11658-025-00822-7
[5]	Zhang H, Cai D, Bai X. Macrophages regulate the progression of osteoarthritis[J]. Osteoarthritis Cartilage, 2020, 28(5): 555-561. doi: 10.1016/j.joca.2020.01.007
[6]	Wang H, Ning W, Liu Y, et al. Photobiomodulation mitigates chondrocyte catabolism in osteoarthritis by modulating macrophage M1 polarization through the IL-6/JAK/STAT pathway[J]. J Orthop Surg Res, 2025, 20(1): 1082. doi: 10.1186/s13018-025-06506-4
[7]	Zhang F, Wu W, Yuan Y, et al. CSF1 regulates inflammation and apoptosis in intervertebral disc degeneration[J]. Sci Rep, 2026, 16(1): 10566. doi: 10.1038/s41598-026-44984-6
[8]	Sheng K, Bisson D G, Saran N, et al. The TLR-M-CSF axis is implicated in increased bone turnover and curve progression in adolescent idiopathic scoliosis[J]. Arthritis Res Ther, 2025, 27(1): 68. doi: 10.1186/s13075-025-03535-6
[9]	Zheng M, Li Z, Feng Y, et al. The role of CD14 and CSF1R in osteoarthritis and gastritis[J]. Medicine, 2023, 102(43): e35567. doi: 10.1097/MD.0000000000035567
[10]	Hu P, Li B, Yin Z, et al. Multi-omics characterization of macrophage polarization-related features in osteoarthritis based on a machine learning computational framework[J]. Heliyon, 2024, 10(9): e30335. doi: 10.1016/j.heliyon.2024.e30335
[11]	Salti T, Braunstein I, Haimovich Y, et al. Widespread S-persulfidation in activated macrophages as a protective mechanism against oxidative-inflammatory stress[J]. Redox Biol, 2024, 72: 103125. doi: 10.1016/j.redox.2024.103125
[12]	Piccioni G, Maisto N, D’Ettorre A, et al. Switch to phagocytic microglia by CSFR1 inhibition drives amyloid-beta clearance from glutamatergic terminals rescuing LTP in acute hippocampal slices[J]. Transl Psychiatry, 2024, 14: 338. doi: 10.1038/s41398-024-03019-2
[13]	Zheng M, Zhu Y, Wei K, et al. Metformin attenuates the inflammatory response via the regulation of synovial M1 macrophage in osteoarthritis[J]. Int J Mol Sci, 2023, 24(6): 5355. doi: 10.3390/ijms24065355
[14]	Lopa S, Libonati F, Mareschi K, et al. Using macrophage polarization in human platelet lysate to test the immunomodulatory potential of cells for clinical use[J]. Biomedicines, 2024, 12(4): 833. doi: 10.3390/biomedicines12040833
[15]	Fu S, Du H, Ling X, et al. Suppressing chondrocyte cuproptosis by syringaresinol-4-O-β-d-glucoside alleviates gouty arthritis[J]. Front Pharmacol, 2025, 16: 1565422. doi: 10.3389/fphar.2025.1565422
[16]	Xu M, Sun X, Ma X, et al. Sodium tanshinone IIA sulfonate alleviates osteoarthritis through targeting SIRT1[J]. Chin Med, 2025, 20(1): 142. doi: 10.1186/s13020-025-01166-2
[17]	Li X, Cheng Y, Gu P, et al. Engineered microchannel scaffolds with instructive niches reinforce endogenous bone regeneration by regulating CSF-1/CSF-1R pathway[J]. Adv Mater, 2024, 36(19): e2310876. doi: 10.1002/adma.202310876
[18]	Inoue K, Qin Y, Xia Y, et al. Bone marrow Adipoq-lineage progenitors are a major cellular source of M-CSF that dominates bone marrow macrophage development, osteoclastogenesis, and bone mass[J]. eLife, 2023, 12: e82118. doi: 10.7554/eLife.82118
[19]	Kim H J, Kang W Y, Seong S J, et al. Follistatin-like 1 promotes osteoclast formation via RANKL-mediated NF-κB activation and M-CSF-induced precursor proliferation[J]. Cell Signal, 2016, 28(9): 1137-1144. doi: 10.1016/j.cellsig.2016.05.018
[20]	Kitaura H, Zhou P, Kim H J, et al. M-CSF mediates TNF-induced inflammatory osteolysis[J]. J Clin Invest, 2005, 115(12): 3418-3427. doi: 10.1172/JCI26132
[21]	Zeijlon L, Budhwar S, Lindau R, et al. Human amnion epithelial cells induce M2 macrophage polarisation partially via M-CSF secretion but independently of extracellular vesicles in vitro[J]. Front Immunol, 2026, 17: 1723968. doi: 10.3389/fimmu.2026.1723968
[22]	Yuan Y, Li Y, Zhao W, et al. WNT4 promotes macrophage polarization via granulosa cell M-CSF and reduces granulosa cell apoptosis in endometriosis[J]. Cytokine, 2023, 172: 156400. doi: 10.1016/j.cyto.2023.156400
[23]	Wu J J, Sun Z L, Liu S Y, et al. The ASIC3-M-CSF-M2 macrophage-positive feedback loop modulates fibroblast-to-myofibroblast differentiation in skin fibrosis pathogenesis[J]. Cell Death Dis, 2022, 13: 527. doi: 10.1038/s41419-022-04981-9
[24]	Wang Y, Wernersbach I, Strehle J, et al. Early posttraumatic CSF1R inhibition via PLX3397 leads to time- and sex-dependent effects on inflammation and neuronal maintenance after traumatic brain injury in mice[J]. Brain Behav Immun, 2022, 106: 49-66. doi: 10.1016/j.bbi.2022.07.164
[25]	Su S, Liu T, Zheng J Y, et al. Huang Lian Jie Du decoction attenuated colitis via suppressing the macrophage Csf1r/Src pathway and modulating gut microbiota[J]. Front Immunol, 2024, 15: 1375781. doi: 10.3389/fimmu.2024.1375781
[26]	Li X, Zhuang Z, Hao Y, et al. Paeonol relieves chronic neuropathic pain by reducing communication between schwann cells and macrophages in the dorsal root ganglia after injury[J]. Int J Mol Sci, 2025, 26(9): 3964. doi: 10.3390/ijms26093964
[27]	Fujiwara T, Yakoub M A, Chandler A, et al. CSF1/CSF1R signaling inhibitor pexidartinib (PLX3397) reprograms tumor-associated macrophages and stimulates T-cell infiltration in the sarcoma microenvironment[J]. Mol Cancer Ther, 2021, 20(8): 1388-1399. doi: 10.1158/1535-7163.MCT-20-0591
[28]	Adams R C, Carter-Cusack D, Llanes G T, et al. CSF1R inhibition promotes neuroinflammation and behavioral deficits during graft-versus-host disease in mice[J]. Blood, 2024, 143(10): 912-929. doi: 10.1182/blood.2023022040

Relative Articles(20)

Relative Articles

[1]	Xiaotian CHEN, Zhenfei DING, Yining SONG, Banghong JIANG, Fan ZHANG, Yi GAO, Jianzhong GUAN. Mechanisms of miR-21-5p in Promoting Osteoarthritis Progression through Inhibition of SIRT2/AKT Signaling Pathway. Journal of Kunming Medical University, 2026, 47(4): 30-39. doi: 10.12259/j.issn.2095-610X.S20260404
[2]	Jing REN, Yani ZENG, Zhirong SHANG. MiR-346 Inhibits Chondrocyte Proliferation in Idiopathic Short Stature by Targeting SMAD3. Journal of Kunming Medical University, 2026, 47(11): 1-9.
[3]	Peng XU, Yazhou XIAO, Zhengliang LEI, Huan LIU, Luchang LIU. HIF-2Α Promotes Osteoarthritis Progression by Regulating Articular Cartilage Deg-eneration Through Activation of CXCR4. Journal of Kunming Medical University, 2026, 47(5): 37-47. doi: 10.12259/j.issn.2095-610X.S20260504
[4]	Ximeng SONG, Shilong YUAN, Zi'ang LU, Maotong XU. Exploring the Molecular Mechanism of Ligustrazine in Spinal Cord Injury Repair Based on Macrophage Autophagy. Journal of Kunming Medical University, 2025, 46(7): 38-45. doi: 10.12259/j.issn.2095-610X.S20250705
[5]	Haopeng SHENTU, Jing YANG, Weiqing GE, Tao ZHOU, En SONG. The Role of Macrophage Polarization in Thrombotic Diseases. Journal of Kunming Medical University, 2025, 46(1): 1-8. doi: 10.12259/j.issn.2095-610X.S20250101
[6]	Nan HUO, Junbo ZHAO, Min WANG, Weiqiao AN, Cui CUI. The Relationship between M1/M2 Macrophage Expression and the Severity of Diabetes Retinopathy. Journal of Kunming Medical University, 2025, 46(11): 100-106. doi: 10.12259/j.issn.2095-610X.S20251113
[7]	Yilin ZHU, Xiao PENG, Guifu ZHANG, Huinan LONG. Effects of Autophagy on Chondrocyte Apoptosis in Osteoarthritis: An Investigation Based on lncRNA/Hedgehog Signaling Pathway Expression. Journal of Kunming Medical University, 2025, 46(6): 38-45. doi: 10.12259/j.issn.2095-610X.S20250605
[8]	Yihan CHEN, Shanyong ZHANG, Yu DING, Li ZHANG. Research Progress on the Molecular Pathogenesis of Temporomandibular Joint Osteoarthritis. Journal of Kunming Medical University, 2024, 45(7): 1-5. doi: 10.12259/j.issn.2095-610X.S20240701
[9]	Feifei XIE, Yinzi XIN, Min XU, Jinghan LI, Wei WANG. Mechanisms of Long Non-Coding RNAs in Cartilage Development and Related Diseases. Journal of Kunming Medical University, 2024, 45(10): 1-7. doi: 10.12259/j.issn.2095-610X.S20241001
[10]	Zhenxiao ZHANG, Jingjing ZHANG, Yun LIAO, Dandan LI, Heng LI, Longding LIU. Effects of HSV-1 Mutant Strain M6 on Macrophage-Mediated Immune Response after Infecting Human Bronchial Epithelial Cells. Journal of Kunming Medical University, 2024, 45(7): 6-13. doi: 10.12259/j.issn.2095-610X.S20240702
[11]	Shaoyou DENG, Rong LI, Jintao LI, Yulan ZHAO, Peijin WANG, Hong ZHENG. Mechanism of Osteoking Improving Osteoarthritis based on Network Pharmacology and DDM Rats. Journal of Kunming Medical University, 2023, 44(7): 34-39. doi: 10.12259/j.issn.2095-610X.S20230701
[12]	Wenli HUANGFU, Yao HUANG, Bo LIU, Changhai LV, Juan LIU, Zichao DAI. Comparison of Two Induction Methods of Temporo-mandibular Joint Osteoarthritis in Rat Models. Journal of Kunming Medical University, 2023, 44(3): 49-53. doi: 10.12259/j.issn.2095-610X.S20230308
[13]	Liang ZHANG, Baoquan WANG, Xifeng LEI, Xu WANG, Yang KE, Wei ZHANG. M2 Macrophage-derived Exosome miR-1246 Regulates the Growth and Invasion of Gastric Cancer Cells. Journal of Kunming Medical University, 2023, 44(7): 69-77. doi: 10.12259/j.issn.2095-610X.S20230724
[14]	Zihan WANG, Gaiying YE, Tao ZHAO, Jun ZHANG, Yu HU. Experimental Study on the Expression of mTOR in TMJOA Condylar Cartilage of SD Rats. Journal of Kunming Medical University, 2022, 43(10): 10-15. doi: 10.12259/j.issn.2095-610X.S20221033
[15]	Weijia ZHAO, Hongbin LI, Zonghan CHEN. Effects of Micafungin on the Activity of Candida Smooth in Macrophages. Journal of Kunming Medical University, 2022, 43(1): 14-19. doi: 10.12259/j.issn.2095-610X.S20220142
[16]	Yan Hui Ling , Zhao Hong Bin , Qian Chuan Yun , Wang Ying Zhong , Zhang Yang , Shen Xiang Lin , Jiang Gang , Gao Shuang . . Journal of Kunming Medical University, 2019, 40(01): 123-127.
[17]	Xie Yuan Run . Experimental Study on The Chemotaxis of Blood Monocyte to Three Kinds of Glioma Cell Lines(U87,U251 and T98G) in Vitro. Journal of Kunming Medical University,
[18]	Dai Long Jin . . Journal of Kunming Medical University,
[19]	Shi Zhao Kun . . Journal of Kunming Medical University,
[20]	Wang Wei . . Journal of Kunming Medical University,