miR‑217 inhibits osteogenic differentiation of rat bone marrow‑derived mesenchymal stem cells by binding to Runx2.
The elucidation of the underlying molecular mechanisms regulating the osteogenic differentiation of bone marrow‑derived mesenchymal stem cells (BMSCs) is of great importance in improving the treatment of bone‑associated diseases. MicroRNAs (miRNAs) have been proven to regulate the osteogenic differentiation of BMSCs. The present study investigated the role of miR‑217 in the osteogenic differentiation of rat BMSCs. It was observed that miR‑217 expression levels were downregulated during the process of osteogenic differentiation. Subsequently, a dual‑luciferase reporter gene assay demonstrated that miR‑217 targets a putative binding site in the 3'‑untranslated region of the runt related transcription factor 2 (Runx2) gene, which is a key transcription factor for osteogenesis. It was then demonstrated that overexpression of miR‑217 attenuated the osteogenesis of BMSCs and downregulated the expression of Runx2, whereas inhibition of miR‑217 promoted osteoblastic differentiation and upregulated Runx2 expression. Furthermore, the extracellular signal‑regulated kinase (ERK) and p38 mitogen‑activated protein kinase (p38 MAPK) signaling pathways were investigated during osteogenic induction, and the data indicated that miR‑217 may exert a negative effect on the osteogenic differentiation of BMSCs through alteration of ERK and p38 MAPK phosphorylation. The present study therefore concluded that miR‑217 functions as a negative regulator of BMSC osteogenic differentiation via the inhibition of Runx2 expression, and the underlying molecular mechanisms may partially be attributed to mediation by the ERK and p38 MAPK signaling pathways.
Department of Orthopedics, Sheyang County People's Hospital, Yancheng, Jiangsu 224300, P.R. China.
Yu-Long
YL
Zhu
Department of Orthopedics, Sheyang County People's Hospital, Yancheng, Jiangsu 224300, P.R. China.
Shui
S
Wang
Department of Orthopedics, Sheyang County People's Hospital, Yancheng, Jiangsu 224300, P.R. China.
De-Gang
DG
Ding
Department of Orthopedics, Sheyang County People's Hospital, Yancheng, Jiangsu 224300, P.R. China.
Liang
L
Xu
Department of Orthopedics, Sheyang County People's Hospital, Yancheng, Jiangsu 224300, P.R. China.
Hai-Tao
HT
Zhu
D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000070416:Antagomirs; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; C000623105:MIRN217 microRNA, rat; D035683:MicroRNAs; C493717:Runx2 protein, rat; D015675:Osteocalcin; D053495:Osteopontin; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases