miR-296-3p Controls Osteogenic Proliferation and Differentiation by Targeting ICAT and Is Involved in Fracture Healing

Xu, Feng; Huang, Kun; Ji, Wenjun; Huang, Miao; Sima, Jincheng; Li, Jin; Song, Hao; Xiong, Wei; Tian, Zhong

doi:10.14712/fb2025071020064

Fol. Biol. 2025, 71, 64-72

https://doi.org/10.14712/fb2025071020064

miR-296-3p Controls Osteogenic Proliferation and Differentiation by Targeting ICAT and Is Involved in Fracture Healing

Feng Xu¹

, Kun Huang²

, Wenjun Ji³, Miao Huang³, Jincheng Sima³, Jin Li³, Hao Song³, Wei Xiong³

, Zhong Tian⁴

¹Department of Orthopedics, The 943rd Hospital, Joint Logistic Support Force of Chinese People’s Liberation Army, Wuwei, China
²Department of Emergency, Nantong Haimen District People’s Hospital, Nantong, China
³Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
⁴Department of Orthopedics, Chonggang General Hospital, Chongqing, China

Received November 2024
Accepted April 2025

Fragility fractures have been a cause for concern because of their high incidence. For the prevention and treatment of osteoporotic fractures, it is important to understand how to promote bone formation and increase bone mass. This study investigated miR-296-3p expression and function in fragility fracture. The study enrolled 98 patients with hip fractures, 90 patients with wrist fractures and 35 healthy controls. RT-qPCR was used to detect the miR-296-3p level changes before and after surgery in fracture patients and during the differentiation of human bone mesenchymal stem cells (BMSCs). The starBase bioinformatics database was used for prediction of the miR-296-3p target gene, and dual luciferase report was used for verification of the target relationship. Our results demonstrated that miR-296-3p levels are up-regulated in fracture patients, while they gradually decrease during human BMSC differentiation. The up-regulation of miR-296-3p inhibited the proliferation and differentiation ability of human BMSCs, while inhibition of its expression had the opposite effects. miR-296-3p negatively regulates osteogenic differentiation, and over-expression of inhibitor of β-catenin and TCF (ICAT) could counteract the negative regulatory effect. miR-296-3p targets ICAT and affects the expression of key proteins in the Wnt/β-catenin signalling pathway. In conclusion, miR-296-3p can regulate the division and differentiation of osteoblasts by affecting the expression of ICAT and participate in fracture healing.