MicroRNA‑92a overexpression promotes the osteogenic differentiation of bone mesenchymal stem cells by impeding Smad6‑mediated runt‑related transcription factor 2 degradation

Abstract Space flight-induced bone loss has been attributed to a decrease in osteoblast function, without a significant change in bone resorption. To determine the effect of microgravity (MG) on bone, we used the Rotary Cell Culture System [developed by the National Aeronautics and Space Administration (NASA)] to model MG. Cultured mouse calvariae demonstrated a 3-fold decrease in alkaline phosphatase (ALP) activity and failed to mineralize after 7 d of MG. ALP and osteocalcin gene expression were also decreased. To determine the effects of MG on osteoblastogenesis, we cultured human mesenchymal stem cells (hMSC) on plastic microcarriers, and osteogenic differentiation was induced immediately before the initiation of modeled MG. A marked suppression of hMSC differentiation into osteoblasts was observed because the cells failed to express ALP, collagen 1, and osteonectin. The expression of runt-related transcription factor 2 was also inhibited. Interestingly, we found that peroxisome proliferator-activated receptor γ (PPARγ2), which is known to be important for adipocyte differentiation, adipsin, leptin, and glucose transporter-4 are highly expressed in response to MG. These changes were not corrected after 35 d of readaptation to normal gravity. In addition, MG decreased ERK- and increased p38-phosphorylation. These pathways are known to regulate the activity of runt-related transcription factor 2 and PPARγ2, respectively. Taken together, our findings indicate that modeled MG inhibits the osteoblastic differentiation of hMSC and induces the development of an adipocytic lineage phenotype. This work will increase understanding and aid in the prevention of bone loss, not only in MG but also potentially in age-and disuse-related osteoporosis.

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Faculty Opinions recommendation of Effects of a miR-31, Runx2, and Satb2 regulatory loop on the osteogenic differentiation of bone mesenchymal stem cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717991438.793510128 ◽

2015 ◽

Author(s):

Di Chen

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Bone Mesenchymal Stem Cells ◽

Regulatory Loop

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Quercetin promotes osteogenic differentiation and antioxidant responses of mouse bone mesenchymal stem cells through activation of the AMPK / SIRT1 signaling pathway

Phytotherapy Research ◽

10.1002/ptr.7010 ◽

2021 ◽

Author(s):

Nan Wang ◽

Luyao Wang ◽

Jihao Yang ◽

Zhihong Wang ◽

Liangxing Cheng

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Signaling Pathway ◽

Bone Mesenchymal Stem Cells ◽

Antioxidant Responses

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MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta

Scientific Reports ◽

10.1038/s41598-021-87298-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kulisara Marupanthorn ◽

Chairat Tantrawatpan ◽

Pakpoom Kheolamai ◽

Duangrat Tantikanlayaporn ◽

Sirikul Manochantr

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Transcription Factor ◽

Osteogenic Differentiation ◽

Differentiation Potential ◽

Osteogenic Gene Expression ◽

Osteogenic Gene

AbstractMesenchymal stem cells (MSCs) are important in regenerative medicine because of their potential for multi-differentiation. Bone marrow, chorion and placenta have all been suggested as potential sources for clinical application. However, the osteogenic differentiation potential of MSCs derived from chorion or placenta is not very efficient. Bone morphogenetic protein-2 (BMP-2) plays an important role in bone development. Its effect on osteogenic augmentation has been addressed in several studies. Recent studies have also shown a relationship between miRNAs and osteogenesis. We hypothesized that miRNAs targeted to Runt-related transcription factor 2 (Runx-2), a major transcription factor of osteogenesis, are responsible for regulating the differentiation of MSCs into osteoblasts. This study examines the effect of BMP-2 on the osteogenic differentiation of MSCs isolated from chorion and placenta in comparison to bone marrow-derived MSCs and investigates the role of miRNAs in the osteogenic differentiation of MSCs from these sources. MSCs were isolated from human bone marrow, chorion and placenta. The osteogenic differentiation potential after BMP-2 treatment was examined using ALP staining, ALP activity assay, and osteogenic gene expression. Candidate miRNAs were selected and their expression levels during osteoblastic differentiation were examined using real-time RT-PCR. The role of these miRNAs in osteogenesis was investigated by transfection with specific miRNA inhibitors. The level of osteogenic differentiation was monitored after anti-miRNA treatment. MSCs isolated from chorion and placenta exhibited self-renewal capacity and multi-lineage differentiation potential similar to MSCs isolated from bone marrow. BMP-2 treated MSCs showed higher ALP levels and osteogenic gene expression compared to untreated MSCs. All investigated miRNAs (miR-31, miR-106a and miR148) were consistently downregulated during the process of osteogenic differentiation. After treatment with miRNA inhibitors, ALP activity and osteogenic gene expression increased over the time of osteogenic differentiation. BMP-2 has a positive effect on osteogenic differentiation of chorion- and placenta-derived MSCs. The inhibition of specific miRNAs enhanced the osteogenic differentiation capacity of various MSCs in culture and this strategy might be used to promote bone regeneration. However, further in vivo experiments are required to assess the validity of this approach.

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Evaluation of osteogenesis and angiogenesis of icariin loaded on micro/nano hybrid structured hydroxyapatite granules as a local drug delivery system for femoral defect repair

Journal of Materials Chemistry B ◽

10.1039/c5tb00621j ◽

2015 ◽

Vol 3 (24) ◽

pp. 4871-4883 ◽

Cited By ~ 20

Author(s):

Yuqiong Wu ◽

Lunguo Xia ◽

Yuning Zhou ◽

Wudi Ma ◽

Na Zhang ◽

...

Keyword(s):

Drug Delivery ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Drug Delivery System ◽

Local Drug Delivery ◽

Bone Mesenchymal Stem Cells ◽

Femoral Defect ◽

Defect Repair ◽

Local Drug Delivery System

Icariin has been identified to promote osteogenic differentiation of bone mesenchymal stem cells (BMSCs).

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Tenuigenin promotes the osteogenic differentiation of bone mesenchymal stem cells in vitro and in vivo

Cell and Tissue Research ◽

10.1007/s00441-016-2528-1 ◽

2016 ◽

Vol 367 (2) ◽

pp. 257-267 ◽

Cited By ~ 3

Author(s):

Hua-ji Jiang ◽

Xing-gui Tian ◽

Shou-bin Huang ◽

Guo-rong Chen ◽

Min-jun Huang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Bone Mesenchymal Stem Cells

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Three-dimensional porous graphene nanosheets synthesized on the titanium surface for osteogenic differentiation of rat bone mesenchymal stem cells

Carbon ◽

10.1016/j.carbon.2017.09.064 ◽

2017 ◽

Vol 125 ◽

pp. 227-235 ◽

Cited By ~ 16

Author(s):

Jiajun Qiu ◽

Jingshu Guo ◽

Hao Geng ◽

Wenhao Qian ◽

Xuanyong Liu

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Titanium Surface ◽

Graphene Nanosheets ◽

Three Dimensional ◽

Bone Mesenchymal Stem Cells ◽

Porous Graphene ◽

Rat Bone

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Long Noncoding RNA FAM83H-AS1 Modulates SpA-Inhibited Osteogenic Differentiation in Human Bone Mesenchymal Stem Cells

Molecular and Cellular Biology ◽

10.1128/mcb.00362-19 ◽

2019 ◽

Vol 40 (5) ◽

Cited By ~ 3

Author(s):

Haojie Wu ◽

Faqi Cao ◽

Wu Zhou ◽

Gang Wang ◽

Guohui Liu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Noncoding Rna ◽

Ectopic Expression ◽

Bone Destruction ◽

Human Bone ◽

Public Health Care ◽

Bone Mesenchymal Stem Cells ◽

Exact Function

ABSTRACT Osteomyelitis, an infection of the bone and bone marrow, imposes a heavy burden on public health care systems owing to its progressive bone destruction and sequestration. Human bone mesenchymal stem cells (hBMSCs) play a key role in the process of bone formation, and mounting evidence has confirmed that long noncoding RNAs (lncRNAs) are involved in hBMSC osteogenic differentiation. Nevertheless, the exact function and molecular mechanism of lncRNAs in osteogenic differentiation during osteomyelitis development remain to be explored. In this study, hBMSCs were treated with staphylococcal protein A (SpA) during osteogenic differentiation induction to mimic osteomyelitis in vitro. The results of lncRNA microarray analysis revealed that FAM83H-AS1 presented the lowest expression among the significantly downregulated lncRNAs. Functionally, ectopic expression of FAM83H-AS1 contributed to osteogenic differentiation of SpA-induced hBMSCs. Additionally, our findings revealed that FAM83H-AS1 negatively regulated microRNA 541-3p (miR-541-3p), and WNT3A was validated as a target gene of miR-541-3p. Mechanically, FAM83H-AS1 elevated WNT3A expression by competitively binding with miR-541-3p. Lastly, it was demonstrated that FAM83H-AS1/miR-541-3p/WNT3A ameliorated SpA-mediated inhibition of the osteogenic differentiation of hBMSCs, which provided a novel therapeutic strategy for patients with osteomyelitis.

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