miR-34a promotes bone regeneration in irradiated bone defects by enhancing osteoblastic differentiation of mesenchymal stromal cells in rats

Liu, Huan; Dong, Yan; Feng, Xiaoke; Li, Liya; Jiao, Yang; Bai, Shizhu; Feng, Zhihong; Yu, Hao; Li, Xuejian; Zhao, Yimin

doi:10.1186/s13287-019-1285-y

Cited by 36 publications

(26 citation statements)

References 37 publications

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“…It has been confirmed that the abnormal expression of miRNAs is closely related to stem cell differentiation [37]. For instance, miR-34a, miR-450a-5p, and miR-28- 5p have been revealed to be involved in regulating the osteoblastic differentiation of mesenchymal stem cells [38,39]. In BMSCs, the adipogenic and osteogenic differentiation can also be regulated by miR-383 [40], miR-20a-5p [41], and miR-20a-5p [41].…”

Section: Discussionmentioning

confidence: 92%

MiR-596 inhibits osteoblastic differentiation and cell proliferation by targeting Smad3 in steroid-induced osteonecrosis of femoral head

Liu

Lei

2020

J Orthop Surg Res

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Background: It is reported that miR-596 has a potential diagnostic value for non-traumatic osteonecrosis of the femoral head (NOFH), but its underlying mechanisms in NOFH is unclear. Methods: The expression of miR-596 and Smad3 was detected by western blot and quantitative real-time PCR. The relationship between the two molecules was explored using Dual-Luciferase Reporter Assay. Glucocorticoid (GC)dexamethasone, was used to induce bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation, and the effects of miR-596 on BMSC osteogenic differentiation and proliferation were determined.Results: MiR-596 expression was upregulated, while Smad3 expression was inhibited in the bone marrow samples of patients with steroid-induced osteonecrosis of femoral head (SANFH). Overexpression of miR-596 inhibited the proliferation and osteogenic differentiation of BMSCs induced by GC. Meanwhile, the opposite results were observed in the miR-596 inhibitor group. In addition, Smad3 was a target gene of miR-596, and negatively regulated by miR-596. The promotion effect of the miR-596 inhibitor on BMSC proliferation and osteogenic differentiation was reversed by si-Smad3.Conclusion: MiR-596 can suppress GC-BMSC osteoblastic differentiation and proliferation by regulating Smad3 expression.

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Section: Discussionmentioning

confidence: 92%

MiR-596 inhibits osteoblastic differentiation and cell proliferation by targeting Smad3 in steroid-induced osteonecrosis of femoral head

Liu

Lei

2020

J Orthop Surg Res

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“…With regard to skeletal disease treatment, agomiR-130a intravenously injection reduces bone loss in elderly mice by targeting Smurf2 and Pparγ genes [ 137 , 138 ], while collagen-based hydrogel containing agomir-34a elevates bone volume in mouse radiational bone injury area by downregulating Notch1 expression in BMSCs [ 139 ]. In addition, miR-328 is the antagonist of Axin1 gene, whose product AXIN1 protein is an inhibitor of Wnt signaling pathway.…”

Section: Application Of Epigenetic Regulation In Skeletal Diseasesmentioning

confidence: 99%

Epigenetic Regulation in Mesenchymal Stem Cell Aging and Differentiation and Osteoporosis

Wang

Zhu

et al. 2020

Stem Cells International

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Mesenchymal stem cells (MSCs) are a reliable source for cell-based regenerative medicine owing to their multipotency and biological functions. However, aging-induced systemic homeostasis disorders in vivo and cell culture passaging in vitro induce a functional decline of MSCs, switching MSCs to a senescent status with impaired self-renewal capacity and biased differentiation tendency. MSC functional decline accounts for the pathogenesis of many diseases and, more importantly, limits the large-scale applications of MSCs in regenerative medicine. Growing evidence implies that epigenetic mechanisms are a critical regulator of the differentiation programs for cell fate and are subject to changes during aging. Thus, we here review epigenetic dysregulations that contribute to MSC aging and osteoporosis. Comprehending detailed epigenetic mechanisms could provide us with a novel horizon for dissecting MSC-related pathogenesis and further optimizing MSC-mediated regenerative therapies.

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“…6 In another independent study, Liu et al found that miR-34a promotes bone regeneration in irradiated bone defects by enhancing osteoblastic differentiation of BMMSCs in rats. 7 In contrast, Bléry et al reported that the addition of a high concentration of…”

Section: Introductionmentioning

confidence: 96%

Ferulic Acid Promotes Bone Defect Repair After Radiation by Maintaining the Stemness of Skeletal Stem Cells

Liang¹,

Li²,

Wang³

et al. 2021

Stem Cells Translational Medicine

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The reconstruction of irradiated bone defects after settlement of skeletal tumors remains a significant challenge in clinical applications. In this study, we explored radiation-induced skeletal stem cell (SSC) stemness impairments and rescuing effects of ferulic acid (FA) on SSCs in vitro and in vivo. The immunophenotype, cell renewal, cell proliferation, and differentiation of SSCs in vitro after irradiation were investigated. Mechanistically, the changes in tissue regeneration-associated gene expression and MAPK pathway activation in irradiated SSCs were evaluated. The regenerative capacity of SSCs in the presence of FA in an irradiated bone defect mouse model was also investigated. We found that irradiation reduced CD140a-and CD105-positive cells in skeletal tissues and mouse-derived SSCs. Additionally, irradiation suppressed cell proliferation, colony formation, and osteogenic differentiation of SSCs. The RNA-Seq results showed that tissue regeneration-associated gene expression decreased, and the Western blotting results demonstrated the suppression of phosphorylated p38/MAPK and ERK/MAPK in irradiated SSCs. Notably, FA significantly rescued the radiation-induced impairment of SSCs by activating the p38/MAPK and ERK/MAPK pathways. Moreover, the results of imaging and pathological analyses demonstrated that FA enhanced the bone repair effects of SSCs in an irradiated bone defect mouse model substantially. Importantly, inhibition of the p38/MAPK and ERK/MAPK pathways in SSCs by specific chemical inhibitors partially abolished the promotive effect of FA on SSC-mediated bone regeneration. In summary, our findings reveal a novel function of FA in repairing irradiated bone defects by maintaining SSC stemness and suggest that the p38/MAPK and ERK/MAPK pathways contribute to SSC-mediated tissue regeneration postradiation.

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miR-34a promotes bone regeneration in irradiated bone defects by enhancing osteoblastic differentiation of mesenchymal stromal cells in rats

Cited by 36 publications

References 37 publications

MiR-596 inhibits osteoblastic differentiation and cell proliferation by targeting Smad3 in steroid-induced osteonecrosis of femoral head

MiR-596 inhibits osteoblastic differentiation and cell proliferation by targeting Smad3 in steroid-induced osteonecrosis of femoral head

Epigenetic Regulation in Mesenchymal Stem Cell Aging and Differentiation and Osteoporosis

Ferulic Acid Promotes Bone Defect Repair After Radiation by Maintaining the Stemness of Skeletal Stem Cells

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