Osteoclast-derived exosomal miR-378a-3p targets FTO-mediated m6A modification to promote osteogenesis and inhibit osteocyte apoptosis in alcohol-induced osteonecrosis of the femoral head
6 affiliations
- 1The First College of Clinical Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
- 2Department of Orthopedics,The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China
- 3College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong, China
- 4The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
- 5Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
- 6Sanya Hospital of Traditional Chinese Medicine, Sanya, Hainan, China
Abstract
BackgroundAlcohol-induced osteonecrosis of the femoral head (AIONFH) is associated with impaired bone formation and increased bone cell apoptosis. This study investigated the role of osteoclast-derived exosomal miR-378a-3p and the FTO-mediated m6A pathway in AIONFH.MethodsRat bone marrow-derived macrophages (BMMs) were induced to form osteoclasts with or without ethanol. Exosomes were isolated, and differentially expressed miRNAs were identified by sequencing and RT-qPCR. The interaction between miR-378a-3p and FTO was examined using a dual-luciferase reporter assay. The effects of modified osteoclast-derived exosomes on BMSC osteogenic differentiation, apoptosis, FTO expression, and m6A levels were evaluated under ethanol exposure. An AIONFH rat model was used to assess the therapeutic effects of these exosomes in vivo.ResultsEthanol promoted osteoclast formation and reduced miR-378a-3p levels in osteoclast-derived exosomes. miR-378a-3p directly targeted the FTO 3′-UTR and reduced FTO expression. Under ethanol exposure, FTO expression increased, m6A levels decreased, osteogenic differentiation was inhibited, and apoptosis was increased. miR-378a-3p-enriched exosomes reversed these changes by reducing FTO expression, increasing m6A levels, promoting osteogenesis, and reducing apoptosis. In AIONFH rats, these exosomes improved trabecular bone structure, increased osteogenic marker expression, and reduced femoral head apoptosis. Exosomes with miR-378a-3p inhibition produced opposite effects.ConclusionOsteoclast-derived exosomal miR-378a-3p protects against alcohol-induced bone damage by targeting FTO and regulating m6A modification. The miR-378a-3p/FTO/m6A pathway may be a potential therapeutic target for AIONFH.
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BibTeX
@article{zhao2026osteoclastderived,
title = {{Osteoclast-derived exosomal miR-378a-3p targets FTO-mediated m6A modification to promote osteogenesis and inhibit osteocyte apoptosis in alcohol-induced osteonecrosis of the femoral head}},
author = {Canbin Zhao and Jinfu Liu and Jinfu Liu and Dongfeng Chen and Donghui Guan and Liang Guo and Weiwei Wang and Qingyuan Xu and Hongcheng Tao and Chicheng Niu and Bin Sun and Jiang Shao and Ping Zeng},
journal = {Frontiers in Cell and Developmental Biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1975355},
url = {https://doi.org/10.3389/fcell.2026.1975355},
note = {CC BY},
}
RIS
TY - JOUR
TI - Osteoclast-derived exosomal miR-378a-3p targets FTO-mediated m6A modification to promote osteogenesis and inhibit osteocyte apoptosis in alcohol-induced osteonecrosis of the femoral head
AU - Canbin Zhao
AU - Jinfu Liu
AU - Jinfu Liu
AU - Dongfeng Chen
AU - Donghui Guan
AU - Liang Guo
AU - Weiwei Wang
AU - Qingyuan Xu
AU - Hongcheng Tao
AU - Chicheng Niu
AU - Bin Sun
AU - Jiang Shao
AU - Ping Zeng
PY - 2026
DA - 2026/10/26
JO - Frontiers in Cell and Developmental Biology
DO - 10.3389/fcell.2026.1975355
UR - https://doi.org/10.3389/fcell.2026.1975355
AB - BackgroundAlcohol-induced osteonecrosis of the femoral head (AIONFH) is associated with impaired bone formation and increased bone cell apoptosis. This study investigated the role of osteoclast-derived exosomal miR-378a-3p and the FTO-mediated m6A pathway in AIONFH.MethodsRat bone marrow-derived macrophages (BMMs) were induced to form osteoclasts with or without ethanol. Exosomes were isolated, and differentially expressed miRNAs were identified by sequencing and RT-qPCR. The interaction between miR-378a-3p and FTO was examined using a dual-luciferase reporter assay. The effects of modified osteoclast-derived exosomes on BMSC osteogenic differentiation, apoptosis, FTO expression, and m6A levels were evaluated under ethanol exposure. An AIONFH rat model was used to assess the therapeutic effects of these exosomes in vivo.ResultsEthanol promoted osteoclast formation and reduced miR-378a-3p levels in osteoclast-derived exosomes. miR-378a-3p directly targeted the FTO 3′-UTR and reduced FTO expression. Under ethanol exposure, FTO expression increased, m6A levels decreased, osteogenic differentiation was inhibited, and apoptosis was increased. miR-378a-3p-enriched exosomes reversed these changes by reducing FTO expression, increasing m6A levels, promoting osteogenesis, and reducing apoptosis. In AIONFH rats, these exosomes improved trabecular bone structure, increased osteogenic marker expression, and reduced femoral head apoptosis. Exosomes with miR-378a-3p inhibition produced opposite effects.ConclusionOsteoclast-derived exosomal miR-378a-3p protects against alcohol-induced bone damage by targeting FTO and regulating m6A modification. The miR-378a-3p/FTO/m6A pathway may be a potential therapeutic target for AIONFH.
SN - 2296-634X
ER -