Exosomal miR-365a-5p derived from HUC-MSCs regulates osteogenesis in GIONFH through the Hippo signaling pathway

Kuang, Ming-jie; Zhang, Kaihui; Qiu, Jie; Wang, Anbang; Che, Wen-wen; Li, Xiaoming; Shi, Dongli; Wang, Da-Chuan

doi:10.1016/j.omtn.2020.12.006

Cited by 20 publications

(9 citation statements)

References 41 publications

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“…The present study has revealed that HucMSCs-Exos exert a superior regulatory effect on bone metabolism. Specifically, HucMSCs-Exos have been shown to play a pivotal role in enhancing fracture healing through the Wnt signaling pathway [ 34 ], and HucMSCs-Exos derived miR-365a-5p have demonstrated the ability to promote osteogenesis via the Hippo signaling pathway [ 35 ]. Additionally, HucMSCs-Exos have been found to boost the expression of the angiogenic factor vascular endothelial growth factor (VEGF), while exosome-derived miR-21-5p has exhibited the capacity to prevent femoral head necrosis by stimulating angiogenesis and osteogenesis [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

PLGA nanoparticles engineering extracellular vesicles from human umbilical cord mesenchymal stem cells ameliorates polyethylene particles induced periprosthetic osteolysis

Xie,

Hu,

et al. 2023

J Nanobiotechnol

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The wear particle-induced dissolution of bone around implants is a significant pathological factor in aseptic loosening, and controlling prosthetic aseptic loosening holds crucial social significance. While human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exos, Exos) have been found to effectively promote osteogenesis and angiogenesis, their role in periprosthetic osteolysis remains unexplored. To enhance their in vivo application, we engineered HucMSCs-Exos-encapsulated poly lactic-co-glycolic acid (PLGA) nanoparticles (PLGA-Exos). In our study, we demonstrate that PLGA-Exos stimulate osteogenic differentiation while inhibiting the generation of reactive oxygen species (ROS) and subsequent osteoclast differentiation in vitro. In vivo imaging revealed that PLGA-Exos released exosomes slowly and maintained a therapeutic concentration. Our in vivo experiments demonstrated that PLGA-Exos effectively suppressed osteolysis induced by polyethylene particles. These findings suggest that PLGA-Exos hold potential as a therapeutic approach for the prevention and treatment of periprosthetic osteolysis. Furthermore, they provide novel insights for the clinical management of osteolysis.

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Section: Discussionmentioning

confidence: 99%

PLGA nanoparticles engineering extracellular vesicles from human umbilical cord mesenchymal stem cells ameliorates polyethylene particles induced periprosthetic osteolysis

Xie,

Hu,

et al. 2023

J Nanobiotechnol

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“…To investigate the mechanism of action of NONFH exosomes’ impacts on osteogenesis and angiogenesis, we conducted a miRNA sequence. Many differentially expressed miRNAs were identified in exosomes from multiple MSCs and the broad biological significance importance of exosomal miRNAs on osteogenesis and angiogenesis of NONFH has been investigated, including miR-21, miR-26a, miR-148a-3p, miR-451-5p, and miR-365a-5p [ 18 , 21 , 39 – 41 ]. The downstream target genes of these miRNAs include PTEN, PDCD4 PAI-1, and SAV1.…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR-100-5p inhibits osteogenesis of hBMSCs and angiogenesis of HUVECs by suppressing the BMPR2/Smad1/5/9 signalling pathway

Zhu

Yang

et al. 2021

Stem Cell Res Ther

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Background Nontraumatic osteonecrosis of the femoral head (NONFH) is a common, progressive, and refractory orthopaedic disease. Decreased osteogenesis and angiogenesis are considered the main factors in the pathogenesis of NONFH. We aimed to figure out whether exosomes and exosomal miRNA from necrotic bone tissues of patients with NONFH are involved in the pathogenesis of NONFH and reveal the underlying mechanisms. Methods RT-PCR and western blotting (WB) were used to detect the expression of osteogenic, adipogenic, and angiogenic markers. ALP staining and Alizarin Red S (ARS) staining were used to evaluate osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Oil Red O staining was performed to assess the adipocyte deposition. A tube formation assay was used to study angiogenesis of human umbilical vascular endothelial cells (HUVECs). H&E staining and immunohistochemistry (IHC) staining were used to detect the effect of the NONFH exosomes in vivo. MicroRNA sequencing was conducted to identify potential regulators in the NONFH exosomes. The target relationship between miR-100-5p and BMPR2 was predicted and confirmed by a dual luciferase reporter assay and WB. Results The NONFH exosomes reduced the osteogenic differentiation of hBMSCs and angiogenesis of HUVECs. In addition, the injection of the NONFH exosomes caused thinning and disruption of bone trabeculae in the femoral heads of rats. MiR-100-5p expression was upregulated in the NONFH exosomes and inhibited the osteogenesis of hBMSCs and angiogenesis of HUVECs by targeting BMPR2 and suppressing the BMPR2/SMAD1/5/9 signalling pathway. Silencing miR-100-5p expression rescued the reduction in osteogenesis and angiogenesis caused by the NONFH exosomes by activating the BMPR2/SMAD1/5/9 signalling pathway. Conclusion The NONFH exosomal miR-100-5p can lead to NONFH-like damage by targeting BMPR2 and suppressing the BMPR2/SMAD1/5/9 signalling pathway, which may be involved in the pathophysiological mechanisms of nontraumatic osteonecrosis of the femoral head (NONFH).

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“…Regarding GIONFH, miR-21 present in UC-MSCs-EVs was shown to repress dexamethasone-induced apoptosis in osteocytes in vitro and to mediate the prevention of GIONFH in animal models by targeting PTEN, a known inhibitor of the AKT signaling pathway, which in turn promotes cell survival [41]. MiR-365a-5p was also identified as enriched in UC-MSCs-EVs, and being able to induce osteogenesis and proliferation of osteoblasts in GIONFH animal models by targeting SAV1, another key component of the Hippo signaling pathway [42].…”

Section: Evs Derived From Uc-mscsmentioning

confidence: 99%

Educating EVs to Improve Bone Regeneration: Getting Closer to the Clinic

Infante

Alcorta-Sevillano

Macías

et al. 2022

IJMS

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The incidence of bone-related disorders is continuously growing as the aging of the population in developing countries continues to increase. Although therapeutic interventions for bone regeneration exist, their effectiveness is questioned, especially under certain circumstances, such as critical size defects. This gap of curative options has led to the search for new and more effective therapeutic approaches for bone regeneration; among them, the possibility of using extracellular vesicles (EVs) is gaining ground. EVs are secreted, biocompatible, nano-sized vesicles that play a pivotal role as messengers between donor and target cells, mediated by their specific cargo. Evidence shows that bone-relevant cells secrete osteoanabolic EVs, whose functionality can be further improved by several strategies. This, together with the low immunogenicity of EVs and their storage advantages, make them attractive candidates for clinical prospects in bone regeneration. However, before EVs reach clinical translation, a number of concerns should be addressed. Unraveling the EVs’ mode of action in bone regeneration is one of them; the molecular mediators driving their osteoanabolic effects in acceptor cells are now beginning to be uncovered. Increasing the functional and bone targeting abilities of EVs are also matters of intense research. Here, we summarize the cell sources offering osteoanabolic EVs, and the current knowledge about the molecular cargos that mediate bone regeneration. Moreover, we discuss strategies under development to improve the osteoanabolic and bone-targeting potential of EVs.

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Exosomal miR-365a-5p derived from HUC-MSCs regulates osteogenesis in GIONFH through the Hippo signaling pathway

Cited by 20 publications

References 41 publications

PLGA nanoparticles engineering extracellular vesicles from human umbilical cord mesenchymal stem cells ameliorates polyethylene particles induced periprosthetic osteolysis

PLGA nanoparticles engineering extracellular vesicles from human umbilical cord mesenchymal stem cells ameliorates polyethylene particles induced periprosthetic osteolysis

Exosomal miR-100-5p inhibits osteogenesis of hBMSCs and angiogenesis of HUVECs by suppressing the BMPR2/Smad1/5/9 signalling pathway

Educating EVs to Improve Bone Regeneration: Getting Closer to the Clinic

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