miR-346-3p promotes osteoclastogenesis via inhibiting TRAF3 gene
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miR-346-3p promotes osteoclastogenesis via inhibiting TRAF3 gene Yingji Mao 1,2 & Yu Chen 1,3 & Yingxiao Fu 1 & Jingjing Guan 4 & Mengxiang Liang 1 & Yansong Zhu 1 & Fugen Yang 1 & Feixiang Li 1 & Zhe Zhang 1 & Chuanfeng Wan 1 & Pinghui Zhou 2,4 Received: 12 November 2019 / Accepted: 30 June 2020 / Editor: Tetsuji Okamoto # The Society for In Vitro Biology 2020
Abstract MicroRNAs (miRNAs) modulate gene expression and regulate many physiological and pathological conditions. However, their modulation and effect in osteoclastogenesis remain unknown. In this study, we investigated the role of miR-346-3p in regulating the osteoclast differentiation from RAW264.7 cells. We used the miRNA microarray assay, miR-346-3p mimic transfection, tartrate resistant acid phosphatase (TRAP) staining, bone resorption assay, qRT-PCR, and western blot. Our results showed that the expression of miR-346-3p was significantly upregulated during osteoclast differentiation. Further, by transfecting cells with miR-346-3p mimic, we observed an increased number of TRAP-positive multinucleated cells, increased pit area caused by bone resorption, and enhanced expression of osteoclast-specific genes and proteins. Conversely, miR-346-3p inhibition attenuated the osteoclast differentiation and function. Software-mediated prediction and validation using luciferase reporter assay showed that TRAF3, a negative regulator of osteoclast differentiation, was inhibited by miR-346-3p overexpression. Our results showed that miR-346-3p directly targeted TRAF3 mRNA via binding to its 3′-UTR and inhibited the expression of TRAF3 protein. Taken together, our results revealed that miR-346-3p promotes the regulation of osteoclastogenesis by suppressing the TRAF3 gene. In conclusion, miR-346-3p could be a novel therapeutic target for bone loss-related pathogenesis. Keywords miR-346-3p . Osteoclastogenesis . TRAF3 gene
Introduction Ossification mediated by osteoblasts and bone resorption regulated by osteoclasts are the two predominant processes of bone remodeling that also maintain the bone metabolism homeostasis (Boyle et al. 2003). The delicate balance between bone formation and resorption is influenced by a complex network consisting of the immune, vascular, neuroendocrine, and musculoskeletal system (Okamoto et al. 2017). A loss of
Yingji Mao and Yu Chen contributed equally to this work. * Pinghui Zhou [email protected] 1
School of Life Science, Bengbu Medical College, Bengbu 233030, People’s Republic of China
2
Anhui Province Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu 233030, People’s Republic of China
3
Department of Plastic Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People’s Republic of China
4
Department of Orthopedics, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People’s Republic of China
this balance may lead to enhanced bone resorption, which can adversely affect the bone structure and function and may lead to bone disorders, such as rheumatoid arthritis and
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