VDR activation attenuates osteoblastic ferroptosis and senescence by stimulating the Nrf2/GPX4 pathway in age-related osteoporosis

Xu, Pingcui; Lin, Bingfeng; Deng, Xuehui; Huang, Kai; Zhang, Yan; Wang, Nani

doi:10.1016/j.freeradbiomed.2022.11.013

Cited by 45 publications

(8 citation statements)

References 44 publications

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“…And vitamin D may inhibit ferroptosis in pancreatic β-cells through the NFκB-DMT1 signaling pathway [ 205 ]. In addition, the VDR agonist (1,25(OH)2D3) can inhibit ferroptosis in bone cells by activating the Nrf2/GPX4 signaling pathway [ 90 ]. Therefore, vitamin D drugs may protect against DOP development.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have shown that inhibiting ferroptosis in OBs through the Nrf2/GPX4 pathway can improve bone formation capacity and microstructure. Vitamin D receptor (VDR) activators (1,25(OH)2D3) suppress ferroptosis in OBs by activating the Nrf2/GPX4 pathway [ 90 ]. Melatonin can improve bone microstructure both in vivo and in vitro by inhibiting ferroptosis in OBs.…”

Section: Ferroptosis In Opmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Ferroptosis In Opmentioning

confidence: 99%

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis

Chen,

Zhao,

et al. 2024

J Transl Med

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Section: Ferroptosis and Bone-related Diseasesmentioning

confidence: 99%

“…Osteoporosis, a skeletal disorder characterized by changes in bone microstructure, decreased bone density, reduced bone mass, and increased bone fragility leading to fractures, is another bone‐related condition. Xu et al 77 demonstrated that 1,25(OH) 2 D 3 could suppress ferroptosis and cellular senescence in age‐related osteoporosis by activating the Nrf2/GPX4 pathway in osteoblasts via vitamin D receptor (VDR) activation. Conversely, VDR knockout in mice led to osteoblast ferroptosis and inhibition of the Nrf2/GPX4 pathway.…”

Section: The Impact Of Ferroptosis On Certain Skeletal and Neoplastic...mentioning

confidence: 99%

Ferroptosis defense mechanisms: The future and hope for treating osteosarcoma

Ma,

Cong,

Shen

et al. 2024

Cell Biochemistry & Function

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Currently, challenges such as chemotherapy resistance, resulting from preoperative and postoperative chemotherapy, postoperative recurrence, and poor bone regeneration quality, are becoming increasingly prominent in osteosarcoma (OS) treatment. There is an urgent need to find more effective ways to address these issues. Ferroptosis is a novel form of iron‐dependent programmed cell death, distinct from other forms of cell death. In this paper, we summarize how, through the three major defense systems of ferroptosis, not only can substances from traditional Chinese medicine, antitumor drugs, and nano‐drug carriers induce ferroptosis in OS cells, but they can also be combined with immunotherapy, differentiation therapy, and other treatment modalities to significantly enhance chemotherapy sensitivity and inhibit tumor growth. Thus, ferroptosis holds great potential in treating OS, offering more choices and possibilities for future clinical interventions.

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“…103,104 Several studies showed the ability of Nrf2-GPX4, Nrf2-HO-1, AMPK-SIRT1 and other pathways to regulate OB ferroptosis and promote bone-forming. [105][106][107] Tian et al found that ferric ion treatment could promote the increase of ferroptosis indicator NOX4 in MC3T3-E1 cells and also apoptosis indicators: increased caspase-3 and Bax and decreased Bcl-2. 108 Osteoclast differentiation requires the activation of the receptor activator of the nuclear factor-κB (RANK)-RANKL pathway.…”

Section: Ferroptosis and Osteoporosismentioning

confidence: 99%

Targeting Ferroptosis in Bone-Related Diseases: Facts and Perspectives

Chen,

Han,

Wang

et al. 2023

JIR

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Ferroptosis is a new cell fate decision discovered in recent years. Unlike apoptosis, autophagy or pyroptosis, ferroptosis is characterized by iron-dependent lipid peroxidation and mitochondrial morphological changes. Ferroptosis is involved in a variety of physiological and pathological processes. Since its discovery, ferroptosis has been increasingly studied concerning bone-related diseases. In this review, we focus on the latest research progress and prospects, summarize the regulatory mechanisms of ferroptosis, and discuss the role of ferroptosis in the pathogenesis of bone-related diseases, such as osteoporosis (OP), osteoarthritis (OA), rheumatoid arthritis (RA), and osteosarcoma (OS), as well as its therapeutic potential.

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VDR activation attenuates osteoblastic ferroptosis and senescence by stimulating the Nrf2/GPX4 pathway in age-related osteoporosis

Cited by 45 publications

References 44 publications

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis

Ferroptosis defense mechanisms: The future and hope for treating osteosarcoma

Targeting Ferroptosis in Bone-Related Diseases: Facts and Perspectives

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