Interaction between ferroptosis and <scp>TNF</scp>‐α: Impact in obesity‐related osteoporosis

Chen, Xin; Liu, Chao; Yu, Rongcheng; Gan, Ziqi; Zhang, Zhen; Chen, Zhengyuan; Liu, Yuanbo; Wu, Dehai; Yu, Xinyi; Liu, Chu-Feng; Cao, Yang

doi:10.1096/fj.202201958r

Cited by 16 publications

(1 citation statement)

References 89 publications

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“…Similar outcomes have been observed in animal studies. Chen X et al found that rats fed a high-fat diet experienced notable loss of femoral trabecular and cortical bone, possibly due to a more substantial oxidative stress environment in obese rats causing ferroptosis in bone progenitor cells and endothelial cells [ 42 ]. ABSI represents the distribution of abdominal fat, which was used in the study to evaluate the association between central obesity and bone health, and found that central obesity may be more related to bone health than BMI, in which the content of fat and muscle played an important role.…”

Section: Discussionmentioning

confidence: 99%

Central obesity may affect bone development in adolescents: association between abdominal obesity index ABSI and adolescent bone mineral density

Lin,

Tao,

et al. 2024

BMC Endocr Disord

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Purpose Previous studies have suggested that obesity defined by body mass index(BMI) is a protective factor for bone mineral density(BMD), but have overlooked the potential influence of different types of obesity. This study aims to evaluate the correlation between abdominal obesity index A Body Shape Index(ABSI) and adolescent bone density, and analyze the relationship between abdominal obesity and bone metabolism. Methods A total of 1557 adolescent participants were included in NHANES from 2007 to 2018. Calculate the ABSI using a specific formula that takes into account waist circumference and BMI. A weighted multiple linear regression model is used to evaluate the linear correlation between ABSI and BMD. Forest plots are used to analyze the correlations between subgroups, and cubic splines are limited to evaluate the nonlinear correlations and saturation effects between ABSI and BMD. Results After adjusting for confounding factors, there was a significant linear correlation (P < 0.01) between ABSI and femoral BMD, both as a continuous variable and an ordered categorical variable. The restrictive cubic spline curve indicates a significant nonlinear correlation and saturation effect between adolescent ABSI and BMD. Conclusion Research has shown a significant negative correlation between ABSI and BMD at the four detection sites of the femur, and this correlation may vary slightly due to age, race, family income, and different detection sites. The research results indicate that compared to overall body weight, fat distribution and content may be more closely related to bone metabolism.

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Section: Discussionmentioning

confidence: 99%

Central obesity may affect bone development in adolescents: association between abdominal obesity index ABSI and adolescent bone mineral density

Lin,

Tao,

et al. 2024

BMC Endocr Disord

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Picein alleviates oxidative stress and promotes bone regeneration in osteoporotic bone defect by inhibiting ferroptosis via Nrf2/HO‐1/GPX4 pathway

Huang,

Wang,

et al. 2024

Environmental Toxicology

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Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to abnormal oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation, making the OP‐related bone healing a significant clinical challenge. As the osteogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs) is closely related to bone regeneration; currently, this study assessed the effects of Picein on BMSCs in vitro and bone regeneration in osteoporotic bone defect in vivo. Cell viability was determined by CCK‐8 assay. The production of (ROS), malonaldehyde, superoxide dismutase activities, and glutathione was evaluated by using commercially available kits, and a flow cytometry analysis was adopted to detect macrophage polarization. Osteogenic capacity of BMSCs was evaluated by alkaline phosphatase (ALP) activity, ALP staining, and Alizarin red S staining. The expression of osteogenic‐related proteins (OPN, Runx‐2, OCN) and osteogenic‐related genes (ALP, BMP‐4, COL‐1, and Osterix) were evaluated by Western blotting and real‐time PCR (RT‐PCR). In addition, proliferation, migration ability, and angiogenic capacity of human umbilical vein endothelial cells (HUVECs) were evaluated by EdU staining, scratch test, transwell assay, and tube formation assay, respectively. Angiogenic‐related genes (VEGF, vWF, CD31) were also evaluated by RT‐PCR. Results showed that Picein alleviated erastin‐induced oxidative stress, enhanced osteogenic differentiation capacity of BMSCs, angiogenesis of HUVECs, and protects cells against ferroptosis through Nrf2/HO‐1/GPX4 axis. Moreover, Picein regulate immune microenvironment by promoting the polarization of M2 macrophages in vitro. In addition, Picein also reduce the inflammation levels and promotes bone regeneration in osteoporotic bone defect in OP rat models in vivo. Altogether, these results suggested that Picein can promote bone regeneration and alleviate oxidative stress via Nrf2/HO‐1/GPX4 pathway, offering Picein as a novel antioxidant agent for treating osteoporotic bone defect.

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Suppression of Skp2 contributes to sepsis-induced acute lung injury by enhancing ferroptosis through the ubiquitination of SLC3A2

Chen,

Zhang,

Gao

et al. 2024

Cell. Mol. Life Sci.

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Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The inflammatory cytokine storm causes systemic organ damage, especially acute lung injury in sepsis. In this study, we found that the expression of S-phase kinase-associated protein 2 (Skp2) was significantly decreased in sepsis-induced acute lung injury (ALI). Sepsis activated the MEK/ERK pathway and inhibited Skp2 expression in the pulmonary epithelium, resulting in a reduction of K48 ubiquitination of solute carrier family 3 member 2 (SLC3A2), thereby impairing its membrane localization and cystine/glutamate exchange function. Consequently, the dysregulated intracellular redox reactions induced ferroptosis in pulmonary epithelial cells, leading to lung injury. Finally, we demonstrated that intravenous administration of Skp2 mRNA-encapsulating lipid nanoparticles (LNPs) inhibited ferroptosis in the pulmonary epithelium and alleviated lung injury in septic mice. Taken together, these data provide an innovative understanding of the underlying mechanisms of sepsis-induced ALI and a promising therapeutic strategy for sepsis.

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Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis

Cited by 16 publications

References 89 publications

Central obesity may affect bone development in adolescents: association between abdominal obesity index ABSI and adolescent bone mineral density

Central obesity may affect bone development in adolescents: association between abdominal obesity index ABSI and adolescent bone mineral density

Picein alleviates oxidative stress and promotes bone regeneration in osteoporotic bone defect by inhibiting ferroptosis via Nrf2/HO‐1/GPX4 pathway

Suppression of Skp2 contributes to sepsis-induced acute lung injury by enhancing ferroptosis through the ubiquitination of SLC3A2

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