Theranostics 2020; 10(26):12263-12278. doi:10.7150/thno.53009 This issue Cite

Research Paper

Silencing of miR-138-5p sensitizes bone anabolic action to mechanical stimuli

Zhihao Chen1,2#, Fan Zhao1,2#, Chao Liang2,3,6#, Lifang Hu1,2#, Dijie Li1,2, Yan Zhang1,2, Chong Yin1,2, Lei Chen1,2, Luyao Wang2,3, Xiao Lin1,2, Peihong Su1,2, Jianhua Ma1,2, Chaofei Yang1,2, Ye Tian1,2, Wenjuan Zhang1,2, Yu Li1,2, Songlin Peng3,4✉, Weiyi Chen5✉, Ge Zhang2,3✉, Airong Qian1,2✉

1. Lab for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China.
2. Northwestern Polytechnical University - Hong Kong Baptist University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Xi'an, Shaanxi 710072, China.
3. Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR, 999077, China.
4. Department of Spine Surgery, Shenzhen People's Hospital, Southern University of Science and Technology, Jinan University School of Medicine, Shenzhen, 518020, China.
5. Shanxi Key Laboratory of Material Strength & Structural Impact, College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan, 030024, China.
6. Department of Biology, Southern University of Science and Technology, Shenzhen, 518055, China.
#These authors contributed equally to this work.

Citation:
Chen Z, Zhao F, Liang C, Hu L, Li D, Zhang Y, Yin C, Chen L, Wang L, Lin X, Su P, Ma J, Yang C, Tian Y, Zhang W, Li Y, Peng S, Chen W, Zhang G, Qian A. Silencing of miR-138-5p sensitizes bone anabolic action to mechanical stimuli. Theranostics 2020; 10(26):12263-12278. doi:10.7150/thno.53009. https://www.thno.org/v10p12263.htm
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Abstract

Graphic abstract

Emerging evidence is revealing that microRNAs (miRNAs) play essential roles in mechanosensing for regulating osteogenesis. However, no mechanoresponsive miRNAs have been identified in human bone specimens.

Methods: Bedridden and aged patients, hindlimb unloaded and aged mice, and Random Positioning Machine and primary aged osteoblasts were adopted to simulate mechanical unloading conditions at the human, animal and cellular levels, respectively. Treadmill exercise and Flexcell cyclic mechanical stretching were used to simulate mechanical loading in vivo and in vitro, respectively.

Results: Here, we found increased miR-138-5p levels with a lower degree of bone formation in bone specimens from bedridden and aged patients. Loss- and gain-of-function studies showed that miR-138-5p directly targeted microtubule actin crosslinking factor 1 (MACF1) to inhibit osteoblast differentiation under different mechanical conditions. Regarding translational medicine, bone-targeted inhibition of miR-138-5p attenuated the decrease in the mechanical bone anabolic response in hindlimb unloaded mice. Moreover, bone-targeted inhibition of miR-138-5p sensitized the bone anabolic response to mechanical loading in both miR-138-5p transgenic mice and aged mice to promote bone formation.

Conclusion: These data suggest that miR-138-5p as a mechanoresponsive miRNA accounts for the mechanosensitivity of the bone anabolic response and that inhibition of miR-138-5p in osteoblasts may be a novel bone anabolic sensitization strategy for ameliorating disuse or senile osteoporosis.

Keywords: mechanoresponsive, miR-138-5p, sensitize, bone formation, osteoporosis


Citation styles

APA
Chen, Z., Zhao, F., Liang, C., Hu, L., Li, D., Zhang, Y., Yin, C., Chen, L., Wang, L., Lin, X., Su, P., Ma, J., Yang, C., Tian, Y., Zhang, W., Li, Y., Peng, S., Chen, W., Zhang, G., Qian, A. (2020). Silencing of miR-138-5p sensitizes bone anabolic action to mechanical stimuli. Theranostics, 10(26), 12263-12278. https://doi.org/10.7150/thno.53009.

ACS
Chen, Z.; Zhao, F.; Liang, C.; Hu, L.; Li, D.; Zhang, Y.; Yin, C.; Chen, L.; Wang, L.; Lin, X.; Su, P.; Ma, J.; Yang, C.; Tian, Y.; Zhang, W.; Li, Y.; Peng, S.; Chen, W.; Zhang, G.; Qian, A. Silencing of miR-138-5p sensitizes bone anabolic action to mechanical stimuli. Theranostics 2020, 10 (26), 12263-12278. DOI: 10.7150/thno.53009.

NLM
Chen Z, Zhao F, Liang C, Hu L, Li D, Zhang Y, Yin C, Chen L, Wang L, Lin X, Su P, Ma J, Yang C, Tian Y, Zhang W, Li Y, Peng S, Chen W, Zhang G, Qian A. Silencing of miR-138-5p sensitizes bone anabolic action to mechanical stimuli. Theranostics 2020; 10(26):12263-12278. doi:10.7150/thno.53009. https://www.thno.org/v10p12263.htm

CSE
Chen Z, Zhao F, Liang C, Hu L, Li D, Zhang Y, Yin C, Chen L, Wang L, Lin X, Su P, Ma J, Yang C, Tian Y, Zhang W, Li Y, Peng S, Chen W, Zhang G, Qian A. 2020. Silencing of miR-138-5p sensitizes bone anabolic action to mechanical stimuli. Theranostics. 10(26):12263-12278.

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