Extracellular vesicles from human umbilical cord mesenchymal stem cells prevent steroid-induced avascular necrosis of the femoral head via the PI3K/AKT pathway

Peng, Puji; Wang, XueZhong; Qiu, Chen; Zheng, Wendi; Zhang, Hongjun

doi:10.1016/j.fct.2023.114004

Cited by 5 publications

(4 citation statements)

References 55 publications

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“…The inflammatory pathway of receptor activator of nuclear factor NF-kB ligand and macrophage colony-stimulating factor are involved in the pathogenesis of this condition. These factors are necessary for the survival and proliferation of osteoclast precursors; in fact, they signal the cell via their receptor c-Fms, which in turn activates extracellular signal-regulated kinase and phosphoinositide 3-kinase/Akt [72][73][74][75][76][77][78][79]. Non-coding RNAs have been implicated in the pathophysiology of mandibular osteonecrosis, and this information is helpful for diagnosis because these small RANs may be biomarkers of apoptotic activity in bone.…”

Section: Discussionmentioning

confidence: 99%

Highlights on the Effects of Non-Coding RNAs in the Osteonecrosis of the Jaw

Caserta,

Stagno,

Gangemi

et al. 2024

IJMS

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Osteonecrosis of the jaw is the progressive loss and destruction of bone affecting the maxilla or mandible in patients treated with antiresorptive and antiangiogenic agents without receiving prior radiation therapy. The pathogenesis involves the inflammatory pathway of receptor activator of nuclear factor NF-kB ligand and the macrophage colony-stimulating factor, essential for osteoclast precursors survival and proliferation and acting through its receptor c-Fms. Evidence has shown the role of non-coding RNAs in the pathogenesis of osteonecrosis of the jaw and this finding might be useful in diagnosis since these small RNAs could be considered as biomarkers of apoptotic activity in bone. Interestingly, it has been proved that miR-29 and miR-31-5p, acting on specific targets such as CALCR and RhoA, promote programmed-cell death and consequently the necrosis of bone tissue. Specific long non-coding RNAs, instead, have been detected both at reduced levels in patients with multiple myeloma and osteonecrosis, and associated with suppression of osteoblast differentiation, with consequences in the progression of mandible lesions. Among non-coding genic material, circular RNAs have the capability to modify the expression of specific mRNAs responsible for the inhibition of bisphosphonates activity on osteoclastogenesis.

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Section: Discussionmentioning

confidence: 99%

Highlights on the Effects of Non-Coding RNAs in the Osteonecrosis of the Jaw

Caserta,

Stagno,

Gangemi

et al. 2024

IJMS

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“…Glucocorticoids (GCs) are fat-soluble steroid hormones synthesized and released by the hypothalamic-pituitary-adrenal response axis, and can be divided into endogenous GCs and synthetic GCs. [1][2][3] GCs play an essential regulating role in the maintenance of homeostasis and metabolism, as well as the physiologic functions of cardiovascular, central nervous and immune systems, mainly through binding to the glucocorticoid receptor (GR) and activating or inhibiting GR expression. [4] As a member of the nuclear receptor superfamily, GR is primarily located in the cytosol of the cell and then can move into the cell nucleus upon activation.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Glucocorticoid Receptor Binding and Agonist Activities of Typical Glucocorticoids: Insights into Their Endocrine Disrupting Effects

Liang,

Li,

Zhang

et al. 2024

Chemistry & Biodiversity

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Over the past decades, the synthetic glucocorticoids (GCs) have been widely used in clinical practice and animal husbandry. Given the health hazard of these toxic residues in food, it is necessary to explore the detailed interaction mechanisms of typical GCs and their main target glucocorticoid receptor (GR). Hence, this work compared the GR binding and agonist activities of typical GCs. Fluorescence polarization assay showed that these GCs were potent ligands of GR. Their GR binding affinities were in the order of methylprednisolone > betamethasone ≈ prednisolone > dexamethasone, with IC50 values of 1.67, 2.94, 2.95, and 5.58 nM. Additionally, the limits of detection of dexamethasone, betamethasone, prednisolone, and methylprednisolone were 0.32, 0.14, 0.19, and 0.09 μg/kg in fluorescence polarization assay. Reporter gene assay showed that these GCs induced GR transactivation in a dose‐dependent manner, confirming their GR agonist activities. Among which, dexamethasone at the concentration of 100 nM produced a maximal induction of more than 11‐fold over the blank control. Molecular docking and molecular dynamics simulations suggested that hydrogen‐bonding and hydrophobic interactions played an important role in stabilizing the GC‐GR‐LBD complexes. In summary, this work might help to understand the GR‐mediated endocrine disrupting effects of typical GCs.

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Section: Introductionmentioning

confidence: 99%

“…In comparison with live cell injection, EVs do not have the risk of uncontrollable behavior such as cell differentiation, and researchers have confirmed the safety of their intravenous application in animal experiments. 8 EVs derived from various cells have been studied for the treatment of diseases, such as necrosis of the femoral head, 9 chronic heart failure, 10 pulmonary fibrosis, 11 and ulcerative colitis. 12 PE is a placenta-derived disease, and its development mainly includes two stages: 13 leads to insufficient remodeling of the uterine spiral artery, abnormal placental perfusion, and placental dysfunction.…”

Section: ■ Introductionmentioning

confidence: 99%

Extracellular Vesicles Derived from Human Umbilical Cord MSC Improve Vascular Endothelial Function in In Vitro and In Vivo Models of Preeclampsia through Activating Arginine Metabolism

Yu,

Zhang,

Wang

et al. 2023

Mol. Pharmaceutics

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Endothelial cell damage is an important feature of preeclampsia (PE). Human umbilical mesenchymal stem-cell-derived extracellular vesicles (HUMSCs-derived EVs) have been shown to have therapeutic effects on a variety of diseases and tissue damage. However, the therapeutic effect of HUMSCs-derived EVs on endothelial injury in PE remains unclear. This study explored the possible mechanism of HUMSCs-derived EVs in the treatment of endothelial cell injury. Tumor necrosis factor α- and lipopolysaccharide-induced endothelial dysfunction models were used to evaluate the therapeutic effect of HUMSCs-derived EVs on endothelial injury. We further constructed PE mouse models to explore the function of HUMSCs-derived EVs in vivo. The changes of metabolites in endothelial cells after HUMSCs-derived EVs treatment were analyzed by metabolomics analysis and further validated by cell experiments. HUMSCs-derived EVs treatment can alleviate endothelial cell injury in PE, involving cell proliferation, migration, angiogenesis, and anti-inflammatory. Importantly, administration of HUMSCs-derived EVs improves hypertension and proteinuria in PE mice, alleviates kidney damage, and promotes vascularization in the placenta. Furthermore, metabolomics analysis found that the arginine metabolic pathway is activated after HUMSCs-derived EVs treatment. We also observed increased arginine level, nitric oxide content, and nitric oxide synthase activity, and further experiments proved that activating the arginine metabolic pathway could alleviate endothelial dysfunction. Our results reveal that HUMSCs-derived EVs could ameliorate PE endothelial dysfunction by activating the arginine metabolic pathway and may serve as a therapeutic method for treating PE.

show abstract

Extracellular vesicles from human umbilical cord mesenchymal stem cells prevent steroid-induced avascular necrosis of the femoral head via the PI3K/AKT pathway

Cited by 5 publications

References 55 publications

Highlights on the Effects of Non-Coding RNAs in the Osteonecrosis of the Jaw

Highlights on the Effects of Non-Coding RNAs in the Osteonecrosis of the Jaw

Comparison of the Glucocorticoid Receptor Binding and Agonist Activities of Typical Glucocorticoids: Insights into Their Endocrine Disrupting Effects

Extracellular Vesicles Derived from Human Umbilical Cord MSC Improve Vascular Endothelial Function in In Vitro and In Vivo Models of Preeclampsia through Activating Arginine Metabolism

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