Nudt21-mediated alternative polyadenylation of HMGA2 3′-UTR impairs stemness of human tendon stem cell

Sun, Yangbai; Chen, Hua; Ye, Hui; Liang, Wenqing; Lam, Kun-kuan; Cheng, Biao; Jiang, Cen

doi:10.18632/aging.103771

Cited by 10 publications

(14 citation statements)

References 41 publications

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“…RT-PCR was carried out with the CFX96 Real-Time PCR Detection System (Bio-Rad, USA). Total RNA isolation, cDNA synthesis, and gene expression assays were performed as in previous studies [ 29 ]. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an endogenous reference gene.…”

Section: Methodsmentioning

confidence: 99%

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Eugenol-Preconditioned Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Antioxidant Capacity of Tendon Stem Cells In Vitro and In Vivo

Shen

et al. 2022

Oxidative Medicine and Cellular Longevity

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Tendon stem cells (TSCs) are often exposed to oxidative stress at tendon injury sites, which impairs their physiological effect as well as therapeutic application. Recently, extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) were shown to mediate cell protection and survival under stress conditions. The function of BMSC-EVs may be affected by pretreatment with various factors such as eugenol (EUG)—a powerful antioxidant. In our previous study, we found that H2O2 significantly impaired TSC proliferation and tenogenic differentiation capabilities. Apoptosis and intracellular ROS accumulation in TSCs were induced by H2O2. However, such H2O2-induced damage was prevented by treatment with EUG-BMSC-EVs. Furthermore, EUG-BMSC-EVs activated the Nrf2/HO-1 pathway to counteract H2O2-induced damage in TSCs. In a rat patellar tendon injury model, the ROS level was significantly higher than that in the normal tendon and TSCs not pretreated showed a poor therapeutic effect. However, EUG-BMSC-EV-pretreated TSCs significantly improved tenogenesis and matrix regeneration during tendon healing. Additionally, the EUG-BMSC-EV group had a significantly improved fiber arrangement. Overall, EUG-BMSC-EVs protected TSCs against oxidative stress and enhanced their functions in tendon injury. These findings provide a basis for potential clinical use of EUG-BMSC-EVs as a new therapeutic vehicle to facilitate TSC therapies for tendon regeneration.

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Section: Methodsmentioning

confidence: 99%

“…H 2 O 2 and EV Treatments. TSCs were subjected to 0.5 mM H 2 O 2 for up to 24 h as described previously [29]. As soon as cells were exposed to H 2 O 2 , they were incubated in either control medium or medium containing BMSC-EVs 2.11.…”

Section: Internalization Of DII Pkh26-labeled Evs Into Tscsmentioning

confidence: 99%

Eugenol-Preconditioned Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Antioxidant Capacity of Tendon Stem Cells In Vitro and In Vivo

Shen

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…There are reports that NUDT21-mediated Glutaminase isoform switching promotes hematopoietic stem cell metabolism upon stress ( 10 ). In addition, NUDT21-mediated high-mobility AT-hook 2 (HMGA2) 3’-UTR replacement polyadenylic acid damages the stemness of human tendon stem cells ( 11 ). As reported previously, NUDT21 played oncogenic roles in human pancreatic ductal adenocarcinoma cells and leukemia cells ( 12 – 14 ).…”

Section: Introductionmentioning

confidence: 99%

NUDT21 Promotes Tumor Growth and Metastasis Through Modulating SGPP2 in Human Gastric Cancer

Zhu

Zhang

et al. 2021

Front. Oncol.

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Gastric cancer is one of the major malignancies with poor survival outcome. In this study, we reported that NUDT21 promoted cell proliferation, colony formation, cell migration and invasion in gastric cancer cells. The expression levels of NUDT21 were found to be much higher in human gastric cancer tissues compared with normal gastric tissues. NUDT21 expression was positively correlated with tumor size, lymph node metastasis and clinical stage in gastric cancer patients. High level of NUDT21 was associated with poor overall survival (OS) rates in gastric cancer patients. The expression levels of NUDT21 were also much higher in gastric cancer tissues from patients with tumor metastasis compared with those of patients without tumor metastasis. Moreover, forced expression of NUDT21 in gastric cancer cells promoted tumor growth and cell proliferation in xenograft nude mice, and depletion of NUDT21 in gastric cancer cells restrained lung metastasis in vivo. Through high throughput RNA-sequencing, SGPP2 was identified to be positively regulated by NUDT21 and mediated the tumor promoting role of NUDT21 in gastric cancer cells. Therefore, NUDT21 played an oncogenic role in human gastric cancer cells. NUDT21 could be considered as a novel potential target for gastric cancer therapy.

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“…Besides tenocytes, oxidative stress can also reduce the viability, self-renewal and multi-lineage differentiation potential of TDSCs, thereby reducing their regenerative and tenogenic function. In this regard, H 2 O 2 was reported to impair colony formation, stemness marker expression, and differentiation capacity as well as showing suppressed cell migration, cell viability, apoptosis, and proliferation of TDSCs [ 28 , 29 , 30 ]. In a rat patellar tendon window injury model, subcutaneous injection of H 2 O 2 over the tendon was demonstrated to induce more tendon swelling, pain-associated gait asymmetry, disorganized fibrous tissue formation and hypoechogenic areas in tendon tissue, compared to the saline-treated group [ 31 ].…”

Section: Clinical and Pre-clinical Evidence Of Potential Sources And ...mentioning

confidence: 99%

Roles of Oxidative Stress in Acute Tendon Injury and Degenerative Tendinopathy—A Target for Intervention

Lui

Zhang

Yao

et al. 2022

IJMS

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Both acute and chronic tendon injuries are disabling sports medicine problems with no effective treatment at present. Sustained oxidative stress has been suggested as the major factor contributing to fibrosis and adhesion after acute tendon injury as well as pathological changes of degenerative tendinopathy. Numerous in vitro and in vivo studies have shown that the inhibition of oxidative stress can promote the tenogenic differentiation of tendon stem/progenitor cells, reduce tissue fibrosis and augment tendon repair. This review aims to systematically review the literature and summarize the clinical and pre-clinical evidence about the potential relationship of oxidative stress and tendon disorders. The literature in PubMed was searched using appropriate keywords. A total of 81 original pre-clinical and clinical articles directly related to the effects of oxidative stress and the activators or inhibitors of oxidative stress on the tendon were reviewed and included in this review article. The potential sources and mechanisms of oxidative stress in these debilitating tendon disorders is summarized. The anti-oxidative therapies that have been examined in the clinical and pre-clinical settings to reduce tendon fibrosis and adhesion or promote healing in tendinopathy are reviewed. The future research direction is also discussed.

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Nudt21-mediated alternative polyadenylation of HMGA2 3′-UTR impairs stemness of human tendon stem cell

Cited by 10 publications

References 41 publications

Eugenol-Preconditioned Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Antioxidant Capacity of Tendon Stem Cells In Vitro and In Vivo

Eugenol-Preconditioned Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Antioxidant Capacity of Tendon Stem Cells In Vitro and In Vivo

NUDT21 Promotes Tumor Growth and Metastasis Through Modulating SGPP2 in Human Gastric Cancer

Roles of Oxidative Stress in Acute Tendon Injury and Degenerative Tendinopathy—A Target for Intervention

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