MicroRNA-223-3p is involved in fracture healing by regulating fibroblast growth factor receptor 2

Abstract

MicroRNAs (miRNAs) are powerful modulators of fracture healing. The research explored the level of serum miR-223-3p in fracture patients and its potential mechanism in fracture healing. In the study, miR-223-3p levels in 42 patients with intra-articular fracture and 40 patients with hand fracture were detected by real-time fluorescence quantitative PCR reaction (qRT-PCR). Subsequently, osteoblasts MC3T3-E1 was transfected with miR-223-3p mimic or inhibitor, and cell function was detected by Cell counting kit (CCK-8) assay and flow cytometry. Dual-luciferase reporter assay verified the regulation mechanism of miR-223-3p and its target genes. We found that miR-223-3p was significantly elevated over time in patients with intra-articular fracture and hand fracture compared with healthy individuals. Moreover, increased miR-223-3p significantly reduced cell viability and promoted cell apoptosis. The fibroblast growth factor receptor 2 (FGFR2) was the target of miR-223-3p. Serum FGFR2 was significantly decreased in patients, which was contrary to the expression of miR-223-3p. Moreover, FGFR2 levels in cells were negatively regulated by miR-223-3p. Finally, si-FGFR2 significantly reversed the promotion of miR-223-3p inhibitor on cell viability and the inhibition of cell apoptosis. Our research suggested that miR-223-3p is highly expressed in fracture patients, and regulates osteoblast cell viability and apoptosis by targeting FGFR2. This may be a valuable target for fracture healing therapy and provide a new perspective for its treatment.

Knockdown of lncRNA TUG1 alleviates diabetic retinal vascular dysfunction through regulating miR-524-5p/FGFR2

“…The FGFR2 gene encodes a protein that is a member of the fibroblast growth factor receptor (FGFR) family [ 27 ]. FGFR2 was shown to be involved in biological processes such as cell proliferation, migration, tube formation and anti-inflammation in previous studies [ 28 , 29 ]. Our data revealed that overexpression of FGFR2 restored hRMECs function under HG and miR-524-5p overexpression conditions.…”

MicroRNA-223 negatively regulates the osteogenic differentiation of periodontal ligament derived cells by directly targeting growth factor receptors

“…MiR-223 was first identified in haematopoietic cells [ 19 ]. Its abnormal expression in many disorders has been widely studied in recent years [ 20 ]. Previously, miR-223 was reported to be involved in the regulation of infections, immune response and several inflammatory disorders [ 21 ].…”

“…MiR-223 has been proven to be a powerful regulatory RNA in the field of bone biology [ 20 ]. Numerous studies documented the potential function of miR-223 in controlling osteoblast differentiation and stimulating differentiation of osteoclasts [ 15 ].…”

“…In our study, bioinformatics analysis and dual luciferase reporter gene assay revealed that miR-223 interacted with two growth factor receptors (TGFβR2 and FGFR2) and inhibited their genes expression. FGFR2 has been identified as miR-223 target in various cells, such as HEK293T cells [ 27 ], AD-293 cells [ 10 ] and MC3T3-E1 cells [ 20 ]. FGFR2 is a critical regulator of osteoblasts.…”

Human umbilical cord mesenchymal stromal cells promotes the proliferation and osteogenic differentiation of autologous bone marrow stem cells by secreting exosomes

“…The role of osteoblasts is to synthesize bone matrix, which is differentiated from ABMSCs [ 25 , 26 ]. The process of fracture healing requires the production of a large number of new osteoblasts, which accelerates bone synthesis and calcification, and increases bone volume and density [ 27 ]. As the body ages, the number of ABMSCs functional cells decreases, and their potential to differentiate into osteoblasts in the bone marrow is down-regulated [ 28 , 29 ].…”