Inhibition of miR-222-3p activity promoted osteogenic differentiation of hBMSCs by regulating Smad5-RUNX2 signal axis

Yan, Jiang; Guo, Duo; Yang, Shu; Sun, Huaimei; Wu, Bo; Zhou, Dujin

doi:10.1016/j.bbrc.2016.01.133

Cited by 45 publications

(37 citation statements)

References 25 publications

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“…miR-210 and miR-378a promoted osteogenesis in rodent cells, 20,21 which contrasts the inhibitory effects observed in our study employing hBMSCs, whereas miR-34c and miR-146a inhibited osteoblastogenesis in rodent cells, 21,22 which is in agreement with our study. The remaining four were studied in human MSCs; miR-222, miR-31 (also in rats), and miR-138 inhibited osteoblastogenesis, 5,9,[23][24][25] which was consistent with our study, whereas miR-17 upregulated osteoblastogenesis, which is in contrast with our study. 26 These results show that some miRNAs are evolutionary conserved and play a similar role across species such as miR-31 and miR-34c, whereas other miRNAs, such as miR-210 and miR-378a, exhibit species specificity.…”

Section: Discussionsupporting

confidence: 90%

“…13,42 In accordance with this, recent studies have shown that inhibiting miR-222 enhanced osteogenesis in vitro and fracture healing in the femur of rats. 23,24 Cell-cycle regulation is essential for hBMSC self-renewal and growth, and this occurs through the inhibition of cell-cycle inhibitors such as CDKN1B and CDKN1A. 45 Here, we show that CDKN1B is inhibited by miR-222.…”

Section: Discussionmentioning

confidence: 72%

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Global MicroRNA Profiling in Human Bone Marrow Skeletal—Stromal or Mesenchymal–Stem Cells Identified Candidates for Bone Regeneration

et al. 2018

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Bone remodeling and regeneration are highly regulated multistep processes involving posttranscriptional regulation by microRNAs (miRNAs). Here, we performed a global profiling of differentially expressed miRNAs in bone-marrow-derived skeletal cells (BMSCs; also known as stromal or mesenchymal stem cells) during in vitro osteoblast differentiation. We functionally validated the regulatory effects of several miRNAs on osteoblast differentiation and identified 15 miRNAs, most significantly miR-222 and miR-423, as regulators of osteoblastogenesis. In addition, we tested the possible targeting of miRNAs for enhancing bone tissue regeneration. Scaffolds functionalized with miRNA nano-carriers enhanced osteoblastogenesis in 3D culture and retained this ability at least 2 weeks after storage. Additionally, anti-miR-222 enhanced in vivo ectopic bone formation through targeting the cell-cycle inhibitor CDKN1B (cyclin-dependent kinase inhibitor 1B). A number of additional miRNAs exerted additive osteoinductive effects on BMSC differentiation, suggesting that pools of miRNAs delivered locally from an implanted scaffold can provide a promising approach for enhanced bone regeneration.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 72%

Global MicroRNA Profiling in Human Bone Marrow Skeletal—Stromal or Mesenchymal–Stem Cells Identified Candidates for Bone Regeneration

et al. 2018

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“…Smad5, Runx2 Increased in serum of aged patients, (77) and inhibits osteoblastogenesis in vitro in human mesenchymal stem cells. (80)…”

Section: Hsa-mir-20a-5pmentioning

confidence: 99%

Lack of Association Between Select Circulating miRNAs and Bone Mass, Turnover, and Fractures: Data From the OFELY Cohort

Feurer

Kan

Croset

et al. 2019

Journal of Bone and Mineral Research

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Postmenopausal osteoporosis is characterized by the occurrence of fragility fracture with an increase in morbidity and mortality. Recently, microRNAs (miRNAs) have raised interest as regulators of translational repression, mediating a number of key processes, including bone tissue in both physiological and diseased states. The aim of this study was to examine the serum levels of 32 preselected miRNAs with reported function in bone and their association with osteoporotic fracture. We performed cross-sectional and longitudinal analyses from the OFELY Cohort. Serum levels of the miRNAs were quantified by qRT-PCR in 682 women: 99 premenopausal and 583 postmenopausal women, with 1 and 122 women with prevalent fragility fractures in each group, respectively. We have collected clinical variables (such as age, prevalent, and incident fractures), bone turnover markers (BTMs), BMD by dual X-ray absorptiometry, and bone microarchitecture with HRpQCT. We observed a number of miRNAs to be associated with fragility fractures (prevalent or incident), BTMs, BMD, and microarchitecture. This effect, however, was negated after age adjustment. This may be because age was also strongly associated with the serum levels of the 32 miRNAs (correlation coefficient up to 0.49), confirming previous findings. In conclusion, in a well-characterized prospective cohort with a sizeable sample size, we found no evidence that these 32 preselected miRNAs were not associated with BTMs, BMD, microarchitecture, and or fragility fractures. Ã CTX, mg/L (min-max) 0.466 (0.057-1.470) 0.374 (0.107-1.030) 0.481 (0.057-1.470) Ã Osteocalcin, ng/mL (min-max) Ã Ã p value considered as significant if <0.05. Tt.vBMD ¼ total volumetric bone mineral density; Ct.vBMD ¼ cortical volumetric bone mineral density; Tb.vBMD ¼ trabecular volumetric bone mineral density; BAP ¼ bone alkaline phosphatase. Journal of Bone and Mineral Research LACK OF ASSOCIATION BETWEEN miRNAs AND BONE: DATA FROM THE OFELY COHORT 5 FEURER ET AL. Ã Radius Tt.vBMD, mg/cm 3 (min-max) 245.6 (122.9-482.1) 278.1 (101.9-515.8) Ã Radius Ct.vBMD, mg/cm 3 (min-max) 771.9 (556.9-956.4) 803.0 (572.6-1004.8) Ã Radius Tb.vBMD, mg/cm 3 (min-max) 123.2 (50.3-264.0) 141.8 (17.5-262.8) Ã Tibia Tt.vBMD, mg/cm 3 (min-max) 228.3 (124.2-371.2) 252.8 (109.0-417.4) Ã Tibia Ct.vBMD, mg/cm 3 (min-max) 702.6 (437.7-912.7) 744.6 (376.7-976.6) Ã Tibia Tb.vBMD, mg/cm 3 (min-max) 133.6 (52.0-212.6) 149.3 (31.9-254.7) Ã CTX, mg/L (min-max) 0.463 (0.057-1.16) 0.484 (0.062-1.470) NS Osteocalcin, ng/mL (min-max) 28.6 (4.2-90.2) 27.7 (6.5-86.2) NS P1NP, ng/mL (min-max) 49.0 (8.1-138.6) 21.5 (10.0-139.7) NS BAP, UI/L (min-max) 39.3 (15.2-69.4) 38.8 (10.1-88.6) NS Ã p-value considered as significant if <0.05. Tt.vBMD ¼ total volumetric bone mineral density; Ct.vBMD ¼ cortical volumetric bone mineral density; Tb.vBMD ¼ trabecular volumetric bone mineral density; BAP ¼ bone alkaline phosphatase. 8 FEURER ET AL.

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“…A recently study demonstrated that miR-214 represses the osteogenic differentiation of MSCs by inhibiting the FGFR1/FGF signaling pathway [20]. Moreover, suppression of miR-222-3p activity promoted the osteogenic differentiation of hBMSCs through regulating the Smad5-RUNX2 signaling axis [21]. With the development of related studies, miRNAs could probably be applied in bone tissue engineering and disease therapy.…”

Section: Introductionmentioning

confidence: 99%

MiR-125b Regulates the Osteogenic Differentiation of Human Mesenchymal Stem Cells by Targeting BMPR1b

Wang

Xie

Hou

et al. 2017

Cell Physiol Biochem

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Background/Aims: Osteogenic differentiation of mesenchymal stem cells (MSCs) plays a crucial role in bone regeneration and bone reparation. This complex process is regulated precisely and firmly by specific factors. Recent studies have demonstrated that miR-125b regulates osteogenic differentiation, but little is known about the molecular mechanisms of this regulation. Furthermore, how miR-125b regulates the osteogenic differentiation of MSCs still needs elucidation. Methods: In the present study, human bone marrow-derived mesenchymal stem cells (hBMSCs) were isolated and induced to osteoblasts with miR-125b inhibition or overexpression. qRT-PCR and western blot analysis were used to detect the expression of osteogenic marker genes and proteins. Alkaline phosphatase (ALP) and Alizarin Red (ARS) staining were performed to evaluate the osteoblast phenotype. TargetScan, PicTar and miRanda database were used to predict the target gene of miR-125b. Dual luciferase reporter assay and RNA interference were performed to verify the target gene. Micro-CT imaging and histochemical staining were used to investigate the bone defect repair capacity of miR-125b in vivo. Results: We observed that miR-125b was expressed at a low level during the osteogenic differentiation of hBMSCs. Then, we found that osteogenic marker genes were negatively regulated by miR-125b during the course of osteogenic differentiation, suggesting that miR-125b down regulation plays an important role in the process of osteogenic differentiation. Bioinformatics approaches using miRNA target prediction algorithms indicated that the bone morphogenetic protein type Ib receptor (BMPR1b) is a potential target of miR-125b. The results of the dual luciferase reporter assay indicated that miR-125b binds to the 3’-UTR of the BMPR1b gene. We observed that knockdown of BMPR1b by siRNA inhibited the osteogenic differentiation of hBMSCs. Furthermore, by co-transfecting cells with an miR-125b inhibitor and si-BMPR1b, we found that the osteogenic capacity of the cells transfected with miR-125b inhibitor was blocked upon knockdown of BMPR1b. In vivo, demineralized bone matrix (DBM) was composited with hBMSCs as a scaffold to repair segmental femoral defects. By inhibiting the expression of miR-125b, hBMSCs showed a better capacity to repair bone defects. Conclusions: Taken together, our study demonstrated that miR-125b regulated the osteogenic differentiation of hBMSCs by targeting BMPR1b and that inhibiting miR-125b expression could enhance the capacity of bone defect repair in vivo.

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Inhibition of miR-222-3p activity promoted osteogenic differentiation of hBMSCs by regulating Smad5-RUNX2 signal axis

Cited by 45 publications

References 25 publications

Global MicroRNA Profiling in Human Bone Marrow Skeletal—Stromal or Mesenchymal–Stem Cells Identified Candidates for Bone Regeneration

Global MicroRNA Profiling in Human Bone Marrow Skeletal—Stromal or Mesenchymal–Stem Cells Identified Candidates for Bone Regeneration

Lack of Association Between Select Circulating miRNAs and Bone Mass, Turnover, and Fractures: Data From the OFELY Cohort

MiR-125b Regulates the Osteogenic Differentiation of Human Mesenchymal Stem Cells by Targeting BMPR1b

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