AUTHOR=Wang Cheng , Wang Peng , Li Feng , Li Yang , Zhao Minwei , Feng Hui , Meng Haoye , Li Junyang , Shi Peng , Peng Jiang , Tian Hua 

TITLE=Adenovirus-associated anti-miRNA-214 regulates bone metabolism and prevents local osteoporosis in rats

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2023.1164252

DOI=10.3389/fbioe.2023.1164252

ISSN=2296-4185

ABSTRACT=<p><bold>Objective:</bold> We investigated the expression of miRNA-214 in human osteoporotic bone tissue and tested the utility of adeno-associated virus (AAV) expressing a miRNA-214 inhibitor in terms of preventing local osteoporosis of the femoral condyle in a rat model of osteoporosis.</p><p><bold>Methods:</bold> (1) Femoral heads of patients who underwent hip replacements at our hospital because of femoral neck fractures were collected and divided into osteoporosis and non-osteoporosis groups based on preoperative bone mineral density data. MiRNA-214 expression was detected in bone tissues exhibiting obvious bone microstructural changes in the two groups. (2) A total of 144 SD female rats were divided into four groups: the Control, Model, Negative control (Model + AAV), and Experimental (Model + anti-miRNA-214) groups. AAV-anti-miRNA-214 was injected locally into the rat femoral condyles; we explored whether this prevented or treated local osteoporosis.</p><p><bold>Results:</bold> (1) MiRNA-214 expression in the human femoral head was significantly increased in the osteoporosis group. (2) Compared to the Model and Model + AAV groups, the bone mineral density (BMD) and femoral condyle bone volume/tissue volume (BV/TV) ratio in the Model + anti-miRNA-214 group were significantly higher; in addition, the number (TB.N) and thickness (TB.Th) of the trabecular bones were increased (all <italic>p</italic> &lt; 0.05). MiRNA-214 expression in the femoral condyles of the Model + anti-miRNA-214 group was significantly higher than that in the other groups. The expression levels of the osteogenesis-related genes <italic>Alp</italic>, <italic>Bglap</italic>, and <italic>Col1α1</italic> increased, while those of the osteoclast-related genes <italic>NFATc1</italic>, <italic>Acp5</italic>, <italic>Ctsk</italic>, <italic>Mmp9</italic>, and <italic>Clcn7</italic> decreased.</p><p><bold>Conclusion:</bold> AAV-anti-miRNA-214 promoted osteoblast activity and inhibited osteoclast activity in the femoral condyles of osteoporotic rats, improving bone metabolism and slowing osteoporosis progression.</p>