MicroRNA-29 facilitates transplantation of bone marrow-derived mesenchymal stem cells to alleviate pelvic floor dysfunction by repressing elastin

Jin, Mingzhu; Wu, Yong; Wang, Jun; Ye, Weiping; Wang, Lei; Yin, Peng; Liu, Wei; Pan, Cunhong; Hua, Xiaolin

doi:10.1186/s13287-016-0428-7

Cited by 25 publications

(25 citation statements)

References 28 publications

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“…Our previous results suggested that overexpression of IGF‐1 in BMSCs improved its therapeutic effect in rat uterus injury model 16. Next, we attempted to elucidate the detailed molecular events underlying this process.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous results suggested that overexpression of IGF-1 in BMSCs improved its therapeutic effect in rat uterus injury model. 16 Next, we attempted to elucidate the detailed molecular events underlying this process. It is reported that NF-jB signalling might involve in IL-10 regulation, which prompted us to examine the change of p50 subunit and potential contribution to IL-10 modulation in response to IGF-1 overexpression.…”

Section: Igf-1 Improved Bmscs Transplant Therapy In Rat Uterus Injurymentioning

confidence: 99%

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Transplant of insulin‐like growth factor‐1 expressing bone marrow stem cells improves functional regeneration of injured rat uterus by NF‐κB pathway

Wang

Yang

Jin

et al. 2018

J Cellular Molecular Medi

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To investigate the potential beneficial effect of insulin‐like growth factor‐1 (IGF‐1) in BMSC transplantation therapy of uterus injury and the underlying molecular mechanisms, rat BMSCs were isolated and cultured. The relative expressions of IGF‐1 and IL‐10 were determined by RT‐PCR and immunoblotting. The secretory IL‐10 and released E2 were measured using ELISA kits. The relative vWF and α‐SMA expressions were determined by immunohistochemistry. The direct binding of NF‐κB subunit p50 with IL‐10 promoter was analysed by chromatin immunoprecipitation assay. The regulation of IL‐10 expression by p50 was interrogated by luciferase reporter assay. Our data demonstrated that IGF‐1 expression in BMSCs induced IL‐10 expression and secretion, which was further enhanced by E2‐PLGA. IGF‐1 overexpression improved BMSCs transplantation therapy in rat uterus injury. We further demonstrated that both inhibition and knockdown of p50 abolished IGF‐1‐induced expression and secretion of IL‐10 in BMSCs, which consequently compromised the IGF‐1 conferred therapeutic benefits against uterus injury. Furthermore, we elucidated that p50 regulated IL‐10 expression via direct association with its promoter. Our data suggested that transplantation of IGF‐1 overexpressing BMSCs improved functional regeneration of injured uterus by inducing IL‐10 expression and secretion via activation of NF‐κB signalling.

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Section: Resultsmentioning

confidence: 99%

Section: Igf-1 Improved Bmscs Transplant Therapy In Rat Uterus Injurymentioning

confidence: 99%

Transplant of insulin‐like growth factor‐1 expressing bone marrow stem cells improves functional regeneration of injured rat uterus by NF‐κB pathway

Wang

Yang

Jin

et al. 2018

J Cellular Molecular Medi

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“…A great many of studies highlighted that miR-29a-3p modulate BMSCs proliferation and differentiation. MiR-29a-3p facilitated transplantation of BMSCs to alleviate pelvic floor dysfunction by repressing elastin [ 4 ]. In addition, miR-29a-3p was significantly deregulated in the serum of patients with low bone mass compared with controls [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-29a-3p enhances dental implant osseointegration of hyperlipidemic rats via suppressing dishevelled 2 and frizzled 4

et al. 2018

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BackgroundFine osseointegration is the basis of long-term survival of implant. In our previous study, we observed a strong correlation between hyperlipidemia and compromised osseointegration. MicroRNA-29a-3p (miR-29a-3p) has been discovered to participate in bone marrow mesenchymal stem cells (BMSCs) differentiation. However, the role and the underlying mechanisms of hyperlipidemia and miR-29a-3p in osseointegration still remain obscure.ResultsIn peri-implant bone tissues of hyperlipidemia rats, bone mass, mineralization and bone trabecula formation were weakened. Alkaline phosphatase (ALP) and runt-related transcription factor 2 (Runx2), and miR-29a-3p expression were reduced. While in normal rats, implant-bone interfaces were filled with dense new bone and ALP, Runx2 and miR-29a-3p were up-regulated. Overexpressed miR-29a-3p can reverse the adverse effect of hyperlipidemia on osseointegration. Implants were tightly integrated with the surrounding dense new bone tissues, and ALP as well as Runx2 mRNAs were enhanced in miR-29a-3p overexpressed and hyperlipidemia rats, while little peri-implant bone tissue existed, ALP and Runx2 deregulated on miR-29a-3p inhibited rats. Dishevelled 2 (Dvl2) mRNA was declined in peri-implant bone tissue of high-fat (HF) group than normal group, while frizzled 4 (Fzd4) mRNA declined on day 5 and increased from day 10 to day 20 after implantation in hyperlipidemia rats than in normal rats. Next, BMSCs were cultured under HF or normal medium in vitro. In the HF group, ALP activity and mineralization, ALP and Runx2 mRNAs and proteins expression, and miR-29a-3p expression were suppressed, while adipogenesis was increased, as a result, cytoskeletons were sparse and disordered compared to control group. However, when miR-29a-3p was overexpressed in BMSCs, ALP activity, ALP, Runx2, Dvl2 and Fzd4 mRNAs and proteins expressions were up-regulated. As miR-29a-3p was inhibited in BMSCs, the reverse results were obtained. In addition, promoter assay revealed that miR-29a-3p can directly suppress Wnt/β-catenin pathway related Dvl2 and Fzd4 through binding to their 3′-UTR.ConclusionsMiR-29a-3p facilitated implant osseointegration via targeting Wnt/β-catenin pathway-related Dvl2 and Fzd4. MiR-29a-3p/Dvl2/Fzd4 may serve as a promising therapeutic target for hyperlipidemia osseointegration.

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“…In terms of stem cell therapy, MSCs show a multi-directive differentiation ability, whose loss of regenerative capacity lead to the impaired ability to facilitate tissue repair, thereby increasing morbidity ( 53 ). In terms of aging, taking advantage of the differentiation ability of bone marrow-derived MSCs and their secretory factors, which are beneficial for tissue repair and elastin regeneration ( 54 , 55 ) is now being considered as another alternative for vaginal prolapse to reactivate the stem cells ( 56 ). MSCs are not only able to transdifferentiate into various cell types present in the pelvic tissues and maintain collagen secretion with neovascularization but they can also deliver bioactive molecules to sites of injury to promote fibroblast proliferation and collagen synthesis ( 57 ).…”

Section: Obstacles and Outlookmentioning

confidence: 99%

Cellular senescence: A pathogenic mechanism of pelvic organ prolapse (Review)

et al. 2020

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Pelvic organ prolapse (PoP) is a common symptom of pelvic floor disorders which is characterized by the descent of the uterus, bladder or bowel from their normal anatomical position towards or through the vagina. Among the older population, the incidence of POP increases with age. It is becoming necessary to recognize that POP is a degenerative disease that is correlated with age. In recent years, studies have been performed to improve understanding of the cellular and molecular mechanisms concerning senescent fibroblasts in pelvic tissues, which contribute to the loss of structure supporting the pelvic organs. These mechanisms can be classified into gene and mitochondrial dysfunctions, intrinsic senescence processes, protein imbalance and alterations in stem cells. The present review provides an integrated overview of the current research and concepts regarding POP, in addition to discussing how fibroblasts can be targeted to evade the negative impact of senescence on POP. However, it is probable that other mechanisms that can also cause POP exist during cell senescence, which necessitates further research and provides new directions in the development of novel medical treatment, stem cell therapy and non-surgical interventions for POP.

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MicroRNA-29 facilitates transplantation of bone marrow-derived mesenchymal stem cells to alleviate pelvic floor dysfunction by repressing elastin

Cited by 25 publications

References 28 publications

Transplant of insulin‐like growth factor‐1 expressing bone marrow stem cells improves functional regeneration of injured rat uterus by NF‐κB pathway

Transplant of insulin‐like growth factor‐1 expressing bone marrow stem cells improves functional regeneration of injured rat uterus by NF‐κB pathway

MicroRNA-29a-3p enhances dental implant osseointegration of hyperlipidemic rats via suppressing dishevelled 2 and frizzled 4

Cellular senescence: A pathogenic mechanism of pelvic organ prolapse (Review)

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