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Published on: May 16, 2025
rno-miR-199a-3p-Nedd4 signaling regulates mast cell-dependent peripheral sensitization in osteoarthritis pain
Baitong Liu1, Zhuoyang Chen1, Xinye Luo1
1Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; Key Laboratory of Acupuncture for Senile Disease (Chengdu University of TCM), Ministry of Education/Acupuncture and Chronobiology Key Laboratory of Sichuan Province, Chengdu 610075, China.
Purpose:
Acupoints are fundamental to the efficacy of acupuncture. When the body is diseased, the pressure pain threshold (PPT) of the corresponding acupoints typically exhibits significant changes. Clinically, selecting acupoints with marked PPT changes often enhances therapeutic efficacy. Mast cells are involved in changes in the PPT at acupoints, but the regulatory mechanism remains unclear. We aimed to identify microRNAs (miRNAs) that regulate mast cells to elucidate the mechanisms underlying PPT changes, thereby guiding clinical acupuncture practice.
Methods:
We evaluated changes in PPT and differentially expressed miRNAs at the ST36 acupoint in a rat model of knee osteoarthritis. miRNA agonists and antagonists were injected to observe changes in the PPT at the ST36 acupoint. Subsequently, the functions of differentially expressed miRNA in regulating degranulation and their possible targets of action were evaluated using in vitro and in vivo experiments.
Results:
PPT decreased in knee osteoarthritis (KOA) rats, accompanied by increased degranulation of local skin mast cells. rno-miR-199a-3p played a key role in this process. Overexpression of rno-miR-199a-3p increased mast cell degranulation. Furthermore, the overexpression of neural precursor cell expressed developmentally down-regulated 4 (Nedd4) is suppressed by rno-miR-199a-3p, which modulated mast cells.
Conclusion:
Pathological changes in the body lead to changes in the PPT, manifested by altered local pain thresholds and mast cell degranulation. rno-miR-199a-3p targets Nedd4, leading to mast cell degranulation, which probably underlies this mechanism.
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