Treatment of steroid-induced osteonecrosis of the femoral head using porous Se@SiO2 nanocomposites to suppress reactive oxygen species

Deng, Guoying; Niu, Kerun; Zhou, Feng; Li, Buxiao; Kang, Yingjie; Liu, Xijian; Hu, Junqing; Li, Bo; Wang, Qiugen; Che, Yi; Wang, Qian

doi:10.1038/srep43914

Cited by 27 publications

(39 citation statements)

References 62 publications

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“…BMSCs are used to treat early steroid-induced ONFH [43][44][45] ; their survival and stemness in the bone necrotic area are key to the effectiveness of transplantation 46,47 . Studies have revealed an OS microenvironment in the femoral-head necrotic area in which transplanted BMSCs incur a great deal of stress apoptosis and aging, which seriously limits transplantation effectiveness [11][12][13] . More and more studies have shown that mitochondrial dysfunction and damaged-mitochondria accumulation occur before cell stress apoptosis and senescence [19][20][21][22] .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, after ischemic necrosis of the femoral head, inflammatory cells infiltrate, and the released inflammatory mediators also mediate ROS production by the inflammatory cells. Therefore, after necrosis of the femoral head, a local OS microenvironment forms [8][9][10][11] . In order to further study the effects of OS on BMSCs and then to treat the BMSCs, we used high-concentration H 2 O 2 (1000 μM) to simulate an OS microenvironment 35 .…”

Section: Excessive Accumulation Of Damaged Mitochondria Led To Stressmentioning

confidence: 99%

“…After the femoral head suffers avascular necrosis, an oxidative-stress (OS) microenvironment forms in the osteonecrotic area [8][9][10] . The transplanted BMSCs undergo a great deal of stress-induced apoptosis and senescence in this microenvironment, which limits their efficacy 11,12 .…”

Section: Introductionmentioning

confidence: 99%

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P53 and Parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to promote the repair of early steroid-induced osteonecrosis of the femoral head

et al. 2020

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Survival and stemness of bone marrow mesenchymal stem cells (BMSCs) in osteonecrotic areas are especially important in the treatment of early steroid-induced osteonecrosis of the femoral head (ONFH). We had previously used BMSCs to repair early steroid-induced ONFH, but the transplanted BMSCs underwent a great deal of stressinduced apoptosis and aging in the oxidative-stress (OS) microenvironment of the femoral-head necrotic area, which limited their efficacy. Our subsequent studies have shown that under OS, massive accumulation of damaged mitochondria in cells is an important factor leading to stress-induced apoptosis and senescence of BMSCs. The main reason for this accumulation is that OS leads to upregulation of protein 53 (P53), which inhibits mitochondrial translocation of Parkin and activation of Parkin's E3 ubiquitin ligase, which decreases the level of mitophagy and leads to failure of cells to effectively remove damaged mitochondria. However, P53 downregulation can effectively reverse this process. Therefore, we upregulated Parkin and downregulated P53 in BMSCs. We found that this significantly enhanced mitophagy in BMSCs, decreased the accumulation of damaged mitochondria in cells, effectively resisted stress-induced BMSCs apoptosis and senescence, and improved the effect of BMSCs transplantation on early steroidinduced ONFH.

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Section: Discussionmentioning

confidence: 99%

Section: Excessive Accumulation Of Damaged Mitochondria Led To Stressmentioning

confidence: 99%

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P53 and Parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to promote the repair of early steroid-induced osteonecrosis of the femoral head

et al. 2020

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“…Clinically, BMSCs have been used in the treatment of various diseases, especially in tissue engineering . However, we have found that the clinical application of BMSCs still has problems that need to be solved: oxidative stress (OS) severely limits the survival of BMSCs after transplantation, and seriously affects the transplantation efficacy . OS can produce excessive reactive oxygen species (ROS) in BMSCs, which can peroxidize DNA, protein, lipid, mitochondria, endoplasmic reticulum, and others, and eventually accelerate cell senescence and apoptosis .…”

Section: Introductionmentioning

confidence: 99%

New strategy of bone marrow mesenchymal stem cells against oxidative stress injury via Nrf2 pathway: oxidative stress preconditioning

Zhang

Peng

Zhang

et al. 2019

J of Cellular Biochemistry

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Clinically, bone marrow mesenchymal stem cells (BMSCs) have been used in treatment of many diseases, but the local oxidative stress (OS) of lesion severely limits the survival of BMSCs, which reduces the efficacy of BMSCs transplantation. Therefore, enhancing the anti-OS stress ability of BMSCs is a key breakthrough point. Preconditioning is a common protective mechanism for cells or body. Here, the aim of this study was to investigate the effects of OS preconditioning on the anti-OS ability of BMSCs and its mechanism.Fortunately, OS preconditioning can increase the expression of superoxide dismutase, catalase, NQO1, and heme oxygenase 1 through the nuclear factor erythroid 2-related factor 2 pathway, thereby decreased the intracellular reactive oxygen species (ROS) levels, relieved the damage of ROS to mitochondria, DNA and cell membrane, enhanced the anti-OS ability of BMSCs, and promoted the survival of BMSCs under OS.

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“…The PQ + Se@SiO 2 group was also treated with 1 mg/kg porous Se@SiO 2 nanospheres via intraperitoneal injection every 24 h. The concentration of porous Se@SiO 2 nanospheres was selected according to our previous research. 21 The PQ group and PQ + Se@SiO 2 group were randomly divided into 3 sub-groups according to differing times of examination (24,48 and 72 h) after PQ treatment. The rats were executed at the corresponding time points after injection of sodium pentobarbital (50 mg/kg).…”

Section: Animal Experimentsmentioning

confidence: 99%

Porous Se@SiO<sub>2</sub> nanospheres treated paraquat-induced acute lung injury by resisting oxidative stress

Zhu¹,

Deng²,

Ji³

et al. 2017

IJN

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Acute paraquat (PQ) poisoning is one of the most common forms of pesticide poisoning. Oxidative stress and inflammation are thought to be important mechanisms in PQ-induced acute lung injury (ALI). Selenium (Se) can scavenge intracellular free radicals directly or indirectly. In this study, we investigated whether porous Se@SiO 2 nanospheres could alleviate oxidative stress and inflammation in PQ-induced ALI. Male Sprague Dawley rats and RLE-6TN cells were used in this study. Rats were categorized into 3 groups: control (n=6), PQ (n=18), and PQ + Se@SiO 2 (n=18). The PQ and PQ + Se@SiO 2 groups were randomly and evenly divided into 3 sub-groups according to different time points (24, 48 and 72 h) after PQ treatment. Porous Se@SiO 2 nanospheres 1 mg/kg (in the PQ + Se@SiO 2 group) were administered via intraperitoneal injection every 24 h. Expression levels of reduced glutathione, malondialdehyde, superoxide dismutase, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α and interleukin-1β were detected, and a histological analysis of rat lung tissues was performed. The results showed that the levels of ROS, malondialdehyde, NF-κB, p-NF-κB, tumor necrosis factor-α and interleukin-1β were markedly increased after PQ treatment. Glutathione and superoxide dismutase levels were reduced. However, treatment with porous Se@SiO 2 nanospheres markedly alleviated PQ-induced oxidative stress and inflammation. Additionally, the results from histological examinations and wet-to-dry weight ratios of rat lung tissues showed that lung damage was reduced after porous Se@SiO 2 nanosphere treatment. These data indicate that porous Se@SiO 2 nanospheres may reduce NF-κB, p-NF-κB and inflammatory cytokine levels by inhibiting ROS in PQ-induced ALI. This study demonstrates that porous Se@SiO 2 nanospheres may be a therapeutic method for use in the future for PQ poisoning.

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Treatment of steroid-induced osteonecrosis of the femoral head using porous Se@SiO2 nanocomposites to suppress reactive oxygen species

Cited by 27 publications

References 62 publications

P53 and Parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to promote the repair of early steroid-induced osteonecrosis of the femoral head

P53 and Parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to promote the repair of early steroid-induced osteonecrosis of the femoral head

New strategy of bone marrow mesenchymal stem cells against oxidative stress injury via Nrf2 pathway: oxidative stress preconditioning

Porous Se@SiO<sub>2</sub> nanospheres treated paraquat-induced acute lung injury by resisting oxidative stress

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