ArticleJournal of orthopaedic surgery and research2026
let-7c-5p promotes fracture healing by downregulating CDK8.
Article in Journal of orthopaedic surgery and research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPrevious studies have shown that let-7c-5p is significantly expressed at a lower level in the serum of fracture patients, suggesting that it may play a role in bone repair. Therefore, this study aims to explore how let-7c-5p regulates osteogenic differentiation in tibial fractures.
methodsA total of 80 patients with tibial fractures and 83 healthy individuals were included in this study. The level of let-7c-5p in the serum were detected by RT-qPCR. Osteoblast cell line (MC3T3-E1) were cultured in vitro to induce osteogenic differentiation. RT-qPCR was used to detect the expression of let-7c-5p and osteogenic differentiation markers. The activity of alkaline phosphatase (ALP) was determined using an ALP assay kit. Dual-luciferase reporter gene assay and RNA immunoprecipitation were used to verify the targeting relationship between let-7c-5p and CDK8.
resultsIn the early stage of tibial fractures, the level of let-7c-5p in the patient's serum was significantly lower than that of the control group, and as the healing processes progressed, its level gradually increased. In osteogenic induction, let-7c-5p, the activity of ALP, and the levels of osteogenic markers all increase. Increasing the level of let-7c-5p significantly enhanced the expression of osteogenic markers, while inhibiting its expression would weaken this effect. let-7c-5p directly targeted and negatively regulated the expression of cyclin-dependent kinase 8 (CDK8). Overexpression of CDK8 could reverse the osteogenic effect mediated by let-7c-5p.
conclusionDuring the healing process of tibial fractures, let-7c-5p promotes osteogenic differentiation by inhibiting CDK8, thereby accelerating fracture healing.
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