MicroRNA 98-5p Overexpression Contributes to Delayed Fracture Healing via Targeting BMP-2

MicroRNA 98-5p Overexpression Contributes to Delayed Fracture Healing via Targeting BMP-2

Yuan-Bin Zhang,¹ Xiu-Quan Guo,² Gang-Gang Wang³ and Hai-Bo Pu⁴

¹Department of Orthopaedics, Fuyang TCM Hospital of Orthopedics Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
²Department of Spinal Surgery, Zhucheng People's Hospital, Weifang, Shandong, China
³Department of Hand and Foot Surgery, Zhucheng People's Hospital, Weifang, Shandong, China
⁴Department of Orthopaedics, People's Hospital of Chongqing Hechuan, Chongqing, China

MicroRNAs (miRNAs) are related to the regulation of bone metabolism. Delayed fracture healing (DFH) is a common complication after fracture surgery. The study attempted to examine the role of miR-98-5p and bone morphogenetic protein (BMP)-2 with the onset of DFH. A total of 140 patients with femoral neck fracture were recruited, including 80 cases with normal fracture healing (NFH) and 60 cases with DFH. MC3T3-E1 cells were induced cell differentiation for cell function experiments. Real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to test mRNA levels. Cell proliferation and apoptosis were determined via CCK-8 and flow cytometry assay. Luciferase reporter assay was done to verify the targeted regulatory relationship of miR-98-5p with BMP-2. In comparison with NFH cases, DFH patients owned high levels of serum miR-98-5p and low concentration of BMP-2, and the levels of the two indexes are significantly negatively correlated. Both miR-98-5p and BMP-2 had the ability to predict DFH, while their combined diagnostic value is the highest. BMP-2 was demonstrated to be the target gene of miR-98-5p. Overexpression of BMP-2 reversed the role of miR-98-5p in MC3T3-E1 cell proliferation, apoptosis and differentiation. Increased miR-98-5p and decreased BMP-2 serve as potential biomarkers for the diagnosis of DFH. MiR-98-5p overexpression inhibits osteoblast proliferation and differentiation via targeting BMP-2.

Key words —— biomarker; delayed fracture healing; miR-98-5p/BMP-2; osteoblast differentiation

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Tohoku J. Exp. Med., 2024 May, 263(1), 17-25.

Correspondence: Hai-Bo Pu, Department of Orthopaedics, People's Hospital of Chongqing Hechuan, 1366 Xieran Avenue, South Office, Hechuan District, Chongqing 401520, China.

e-mail: Puhaibo_phb@163.com

Gang-Gang Wang, Department of Hand and Foot Surgery, Zhucheng People's Hospital, 59 South Ring Road, Zhucheng, Weifang, Shandong 262200, China.

e-mail: gg_wang1976@163.com