Synovial fluid and plasma levels of milk fat globule–epidermal growth factor 8 are inversely correlated with radiographic severity of knee osteoarthritis

Chen, Feihu; Líu, Hao; Xia, Jie; Ding, Xinyu; Fan, Jiyang; Zhu, Xiao Feng; Cui, Shengyu; Hong, Yi; Gao, Rufeng; Liu, Wei

doi:10.1177/0300060519862460

Cited by 5 publications

(2 citation statements)

References 39 publications

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“…Tests showed that MFG-E8 can reprogram macrophages to the anti-inflammatory M2 phenotype, relieve apoptosis, reverse cellular oxidative stress and modulate the balance between osteoblasts and osteoclasts 17 – 19 . Moreover, it is reported that MFG-E8 is significantly downregulated in synovial fluid and plasma in OA patients 20 . Nevertheless, the effects of MFG-E8 in OA remain unclear.…”

Section: Introductionmentioning

confidence: 99%

MFG-E8 regulated by miR-99b-5p protects against osteoarthritis by targeting chondrocyte senescence and macrophage reprogramming via the NF-κB pathway

Liu

Pan

et al. 2021

Cell Death Dis

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Milk fat globule-epidermal growth factor (EGF) factor 8 (MFG-E8), as a necessary bridging molecule between apoptotic cells and phagocytic cells, has been widely studied in various organs and diseases, while the effect of MFG-E8 in osteoarthritis (OA) remains unclear. Here, we identified MFG-E8 as a key factor mediating chondrocyte senescence and macrophage polarization and revealed its role in the pathology of OA. We found that MFG-E8 expression was downregulated both locally and systemically as OA advanced in patients with OA and in mice after destabilization of the medial meniscus surgery (DMM) to induce OA. MFG-E8 loss caused striking progressive articular cartilage damage, synovial hyperplasia, and massive osteophyte formation in OA mice, which was relieved by intra-articular administration of recombinant mouse MFG-E8 (rmMFG-E8). Moreover, MFG-E8 restored chondrocyte homeostasis, deferred chondrocyte senescence and reprogrammed macrophages to the M2 subtype to alleviate OA. Further studies showed that MFG-E8 was inhibited by miR-99b-5p, expression of which was significantly upregulated in OA cartilage, leading to exacerbation of experimental OA partially through activation of NF-κB signaling in chondrocytes. Our findings established an essential role of MFG-E8 in chondrocyte senescence and macrophage reprogramming during OA, and identified intra-articular injection of MFG-E8 as a potential therapeutic target for OA prevention and treatment.

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Section: Introductionmentioning

confidence: 99%

MFG-E8 regulated by miR-99b-5p protects against osteoarthritis by targeting chondrocyte senescence and macrophage reprogramming via the NF-κB pathway

Liu

Pan

et al. 2021

Cell Death Dis

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“…However, it is uncertain whether MFG-E8 is expressed in the serum of septic patients. MFG-E8 is highly appreciated in inflammatory diseases, including sepsis, colitis, ischaemia and reperfusion-induced intestinal injuries, for its scavenging role and anti-inflammatory properties 7 – 9 . MFG-E8 performs an anti-inflammatory function mainly by enhancing the clearance of apoptotic cells, but the other mechanisms associated with its role have not been clearly revealed 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

MFG-E8 has guiding significance for the prognosis and treatment of sepsis

Wang

Chen³

et al. 2022

Sci Rep

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Sepsis remains a significant clinical challenge. Ferroptosis is involved in the pathogenesis of sepsis. Ferroptosis is associated with oxidative stress, and excessive oxidative stress is suppressed by milk fat globule epidermal growth factor 8 (MFG-E8) under various conditions. However, the role of MFG-E8 in sepsis-induced ferroptosis and oxidative stress is still unclear. First, we collected blood samples from patients with sepsis and detected the expression of serum MFG-E8. Then, the relationship between serum concentrations of MFG-E8 and disease severity was detected. Finally, the effects of MFG-E8 treatment on ferroptosis and oxidative stress in the livers of septic mice were determined. The expression of serum MFG-E8 in healthy subjects was notably higher than that in septic patients. In addition, when nonsurvivors and survivors of sepsis were compared, MFG-E8 levels were considerably lower in the former. The ROC curve for MFG-E8 was also generated. The area under the curve for MFG-E8 was 0.768 (95% confidence interval [CI] 0.627–0.909, p = 0.003). The patients were separated into two groups based on the MFG-E8 cut-off value of 3.86 ng/mL. According to the Kaplan‒Meier survival analysis, patients with low MFG-E8 levels had a significantly decreased 28-day survival rate compared with patients with high MFG-E8 levels. High MFG-E8 levels were substantially related to a decreased risk of death, as demonstrated by the Cox proportional hazard model that we utilized. In addition, compared with sham mice, septic mice exhibited liver and kidney damage, and MFG-E8 may have protective effects. The survival study indicated that MFG-E8 could effectively improve the survival rate of septic mice. Treatment with MFG-E8 suppresses oxidative stress and ferroptosis in the livers of septic mice. Serum MFG-E8 levels are lower in septic patients and are negatively related to disease severity. Treatment with MFG-E8 suppresses oxidative stress and ferroptosis in the livers of septic mice, contributing to significantly improved survival in septic mice. These findings showed that MFG-E8 could be a new sepsis predictive biomarker. MFG-E8 may have therapeutic potential in the treatment of sepsis.

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Milk fat globule-epidermal growth factor 8 exerts anti-osteoarthritis effects by inhibiting apoptosis and inducing autophagy in mouse chondrocytes

Gao,

Feng,

Chen

et al. 2024

Biochemical and Biophysical Research Communications

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Synovial fluid and plasma levels of milk fat globule–epidermal growth factor 8 are inversely correlated with radiographic severity of knee osteoarthritis

Cited by 5 publications

References 39 publications

MFG-E8 regulated by miR-99b-5p protects against osteoarthritis by targeting chondrocyte senescence and macrophage reprogramming via the NF-κB pathway

MFG-E8 regulated by miR-99b-5p protects against osteoarthritis by targeting chondrocyte senescence and macrophage reprogramming via the NF-κB pathway

MFG-E8 has guiding significance for the prognosis and treatment of sepsis

Milk fat globule-epidermal growth factor 8 exerts anti-osteoarthritis effects by inhibiting apoptosis and inducing autophagy in mouse chondrocytes

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