miR-208a-3p Suppresses Osteoblast Differentiation and Inhibits Bone Formation by Targeting ACVR1

Arfat, Yasir Ali; Basra, Muhammad Asim Raza; Shahzad, Muhammad; Majeed, Kashif; Mahmood, Nasir; Munir, Hina

doi:10.1016/j.omtn.2017.11.009

Cited by 42 publications

(26 citation statements)

References 67 publications

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“…Three-point bending test would distinguish the differences in the mechanical properties of bone, as shown in previous 12,26,39,40 and our present studies. It is known that the mechanical testing of bone is a destructive process.…”

supporting

confidence: 71%

Low‐magnitude vibration induces osteogenic differentiation of bone marrow mesenchymal stem cells via miR‐378a‐3p/Grb2 pathway to promote bone formation in a rat model of age‐related bone loss

Zeng

Bao

et al. 2020

FASEB j.

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The dysfunction of bone marrow mesenchymal stem cells (BMSCs) in osteogenic differentiation is one of the main causes of age‐related bone loss. Our previous studies have shown that low‐magnitude vibration (LMV) induces the osteogenic differentiation of BMSCs derived from ovariectomized osteoporotic rats. To investigate whether LMV promotes osteogenic differentiation of BMSCs and its underlying mechanisms in aged rats, 20‐month‐old female Sprague‐Dawley rats (n = 20) were randomly divided into LMV group (rats were vibrated at 0.3 g and 90 Hz for 30 minutes, once daily, 5 days a week until 12 weeks for subsequent analysis, n = 10), static group (rats were placed in the box on the vibration platform without vibration, n = 10); 6‐month‐old female Sprague‐Dawley rats were used as control (young group, n = 10). The bone mineral density and bone strength of aged rats were significantly decreased compared with the young rats. Furthermore, the primary BMSCs isolated and cultured from the aged rats with the whole‐bone marrow differential pasting method showed a decreased ability in osteogenic differentiation compared with that from the young rats. Then the differentially expressed miRNAs between the aged and young rat‐derived BMSCs were screened by high‐throughput sequencing and verified by qRT‐PCR, and we found that miR‐378a‐3p was significantly downregulated in the aged rat‐derived BMSCs compared with the young rat‐derived BMSCs. By transfecting miRNA mimics and inhibitors, miR‐378a‐3p was confirmed to promote the expression levels of osteogenic genes (Runx2, ALP, Col I, and OCN) and ALP activity of the aged rat‐derived BMSCs. Meanwhile, the expression levels of osteogenic genes and miR‐378a‐3p of aged rat‐derived BMSCs were significantly upregulated by LMV (cells were vibrated at 0.3 g and 90 Hz for 30 minutes a day, until 5 days for subsequent analysis), while the LMV‐induced osteogenic gene expression levels of aged rat‐derived BMSCs were suppressed by miR‐378a‐3p inhibitors. Furthermore, the inhibition of growth factor receptor‐bound protein 2 (Grb2) by miR‐378a‐3p and Grb2‐siRNA promoted the LMV‐induced osteogenic differentiation of aged rat‐derived BMSCs. Additionally, LMV was found to promote bone mineral density and bone strength of aged rats in vivo, as well as upregulating the expression level of miR‐378a‐3p and downregulating the expression level of Grb2 of BMSCs from aged rats. These results suggest that LMV induces osteogenic differentiation of BMSCs through miR‐378a‐3p/Grb2 pathway to improve bone mineral density and mechanical properties in a rat model of age‐related bone loss.

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supporting

confidence: 71%

Low‐magnitude vibration induces osteogenic differentiation of bone marrow mesenchymal stem cells via miR‐378a‐3p/Grb2 pathway to promote bone formation in a rat model of age‐related bone loss

Zeng

Bao

et al. 2020

FASEB j.

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“…Evidence has revealed that miRNAs serve a regulatory role in cell proliferation, differentiation and apoptosis (2)(3)(4)(5). Increasing evidence has also revealed that miRNAs are involved in the regulation of osteoblasts differentiation, bone metabolism and bone formation (14)(15)(16)(17)(18)(19). miR-467g has been demonstrated to prevent new bone regeneration by regulating the indian hedgehog protein/Runx2 signaling pathway (33).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑98‑5p prevents bone regeneration by targeting high mobility group AT‑Hook 2

Zheng

Wang

2019

Exp Ther Med

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MicroRNAs (mRNAs or miRs) serve an important role in the regulation of gene expression. In the present study, the role of miR-98-5p in bone regeneration was determined. Three osteoblast cell models were established, including primary human stem cells (BMMSC), mouse BMMSC's and MC3T3-E1 cells. miR-98-5p expression was determined using reverse transcription-quantitative (RT-q)PCR. Osteoblast markers, including alkaline phosphatase, runt related transcription factor 2 and transcription factor Sp7, were determined using RT-qPCR and western blot analysis, respectively. Alkaline phosphatase activity was determined in the present study and cell proliferation and apoptosis assays were performed. Furthermore, an association between miR-98-5p and high mobility group AT-Hook 2 (HMGA2) was revealed. This association was determined using TargetScan and a dual luciferase reporter assay. The current study demonstrated that miR-98-5p was downregulated during osteogenic differentiation and further demonstrated that HMGA2 may be a direct target of miR-98-5p. The results also demonstrated that miR-98-5p upregulation significantly inhibited the osteogenic differentiation of MC3T3-E1 cells, an effect that was reversed by an increased HMGA2 expression. Additionally, the results revealed that miR-98-5p upregulation inhibited MC3T3-E1 cell viability and induced cell apoptosis and these effects were eliminated by HMGA2 overexpression. In conclusion, miR-98-5p may prevent bone regeneration through inhibiting osteogenic differentiation and osteoblast growth by targeting HMGA2.

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“…miR-208a-3p ACVR1 Osteoblasts miR-208a-3p suppresses osteoblast differentiation and inhibits bone formation by targeting ACVR1. [90] MSCs: mesenchymal stem cells; BMSCs: bone marrow mesenchymal stem cells.…”

Section: Engineering Exosomes As Nanocarrier Formentioning

confidence: 99%

Exosome: A Novel Nanocarrier Delivering Noncoding RNA for Bone Tissue Engineering

Liu

Cao

Zhu

et al. 2020

Journal of Nanomaterials

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Bone growth and metabolism are mainly regulated by a series of intracellular molecules and extracellular stimuli. Exosome, as a nanoscale substance secreted to the outside of the cells, plays an extensive role in intercellular communication. This review provides theoretical references and evidences for further exploration of exosomes as noncoding RNA carriers to regulate bone tissue recovery through the following aspects: (1) basic characteristics of exosomes, (2) research progress of exosomal noncoding RNA in bone tissue engineering, (3) current status and advantages of engineering exosomes as nanocarriers for noncoding RNA delivery, and (4) problems and application prospects of exosome therapy in the field of orthopedics.

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miR-208a-3p Suppresses Osteoblast Differentiation and Inhibits Bone Formation by Targeting ACVR1

Cited by 42 publications

References 67 publications

Low‐magnitude vibration induces osteogenic differentiation of bone marrow mesenchymal stem cells via miR‐378a‐3p/Grb2 pathway to promote bone formation in a rat model of age‐related bone loss

Low‐magnitude vibration induces osteogenic differentiation of bone marrow mesenchymal stem cells via miR‐378a‐3p/Grb2 pathway to promote bone formation in a rat model of age‐related bone loss

MicroRNA‑98‑5p prevents bone regeneration by targeting high mobility group AT‑Hook 2

Exosome: A Novel Nanocarrier Delivering Noncoding RNA for Bone Tissue Engineering

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