Engeletin alleviates erastin-induced oxidative stress and protects against ferroptosis via Nrf2/Keap1 pathway in bone marrow mesenchymal stem cells

Huang, Lei; Bian, Mengxuan; Lu, Shunyi; Wang, Jiayi; Yu, Jieqin; Jiang, Libo; Zhang, Jian

doi:10.1016/j.tice.2023.102040

Cited by 10 publications

(5 citation statements)

References 29 publications

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“…Tocopherol could alleviate ferroptosis of BMSCs via regulating the PI3K/AKT/mTOR axis [ 46 ]. Engeletin could lessen Erastin-caused ferroptosis of BMSCs via Nrf2/Keap1 signaling pathway [ 47 ]. Ebselen could recover osteogenic suppression by blocking ferroptosis of BMSCs [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

CRYAB suppresses ferroptosis and promotes osteogenic differentiation of human bone marrow stem cells via binding and stabilizing FTH1

Tian,

Li,

et al. 2024

Aging

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Background: Bone formation and homeostasis are greatly dependent on the osteogenic differentiation of human bone marrow stem cells (BMSCs). Therefore, revealing the mechanisms underlying osteogenic differentiation of BMSCs will provide new candidate therapeutic targets for osteoporosis. Methods: The osteogenic differentiation of BMSCs was measured by analyzing ALP activity and expression levels of osteogenic markers. Cellular Fe and ROS levels and cell viability were applied to evaluate the ferroptosis of BMSCs. qRT-PCR, Western blotting, and co-immunoprecipitation assays were harnessed to study the molecular mechanism. Results: The mRNA level of CRYAB was decreased in the plasma of osteoporosis patients. Overexpression of CRYAB increased the expression of osteogenic markers including OCN, OPN, RUNX2, and COLI, and also augmented the ALP activity in BMSCs, on the contrary, knockdown of CRYAB had opposite effects. IP-MS technology identified CRYAB-interacted proteins and further found that CRYAB interacted with ferritin heavy chain 1 (FTH1) and maintained the stability of FTH1 via the proteasome mechanism. Mechanically, we unraveled that CRYAB regulated FTH1 protein stability in a lactylation-dependent manner. Knockdown of FTH1 suppressed the osteogenic differentiation of BMSCs, and increased the cellular Fe and ROS levels, and eventually promoted ferroptosis. Rescue experiments revealed that CRYAB suppressed ferroptosis and promoted osteogenic differentiation of BMSCs via regulating FTH1. The mRNA level of FTH1 was decreased in the plasma of osteoporosis patients. Conclusions: Downregulation of CRYAB boosted FTH1 degradation and increased cellular Fe and ROS levels, and finally improved the ferroptosis and lessened the osteogenic differentiation of BMSCs.

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Section: Discussionmentioning

confidence: 99%

CRYAB suppresses ferroptosis and promotes osteogenic differentiation of human bone marrow stem cells via binding and stabilizing FTH1

Tian,

Li,

et al. 2024

Aging

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“…Erastin-induced ferroptosis causes an increase in Nrf2 and a decrease in Keap1 expression in BMSCs, with increased expression of TFR1/FPN1 and decreased expression of GPX4 and SLC7A11. Engeletin (dihydrokaempferol 3-rhamnoside), an effective endogenous antioxidant, inhibits erastin-induced ferroptosis in BMSCs via the Nrf2/Keap1 pathway [ 75 ].…”

Section: Ferroptosis In Opmentioning

confidence: 99%

“…2 Osteoporotic ferroptosis of GPX4 and SLC7A11. Engeletin (dihydrokaempferol 3-rhamnoside), an effective endogenous antioxidant, inhibits erastin-induced ferroptosis in BMSCs via the Nrf2/Keap1 pathway [75].…”

Section: Ferroptosis In Bmscsmentioning

confidence: 99%

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis

Chen,

Zhao,

et al. 2024

J Transl Med

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With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic β-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

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“…2,3 Studies have reported that bone loss diseases are closely related with high levels of reactive oxygen species (ROS) in bone homeostasis. 4,5 Because of the osteogenic differentiation capacity, bone marrow mesenchymal stem cells (BMSCs) play an indispensable role in the process of bone formation. 6 Besides, study has also suggested that BMSCs undergo oxidative stress due to excessive accumulation of ROS generated in osteoporotic bone defect.…”

Section: Introductionmentioning

confidence: 99%

“…The treatment of osteoporotic bone defect is still a major problem due to abnormal oxidative stress levels in the OP environment 2,3 . Studies have reported that bone loss diseases are closely related with high levels of reactive oxygen species (ROS) in bone homeostasis 4,5 . Because of the osteogenic differentiation capacity, bone marrow mesenchymal stem cells (BMSCs) play an indispensable role in the process of bone formation 6 .…”

Section: Introductionmentioning

confidence: 99%

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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Engeletin alleviates erastin-induced oxidative stress and protects against ferroptosis via Nrf2/Keap1 pathway in bone marrow mesenchymal stem cells

Cited by 10 publications

References 29 publications

CRYAB suppresses ferroptosis and promotes osteogenic differentiation of human bone marrow stem cells via binding and stabilizing FTH1

CRYAB suppresses ferroptosis and promotes osteogenic differentiation of human bone marrow stem cells via binding and stabilizing FTH1

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis

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

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