Int J Biol Sci 2022; 18(13):4837-4852. doi:10.7150/ijbs.71411 This issue Cite

Research Paper

MiR-138-5p Targets MACF1 to Aggravate Aging-related Bone Loss

Zhihao Chen1,5#, Ying Huai1#, Gaoyang Chen2, Shuyu Liu1, Yan Zhang1,3, Dijie Li1,4, Fan Zhao1,3, Xiaofeng Chen3, Wenjing Mao1, Xuehao Wang1, Chong Yin1, Chaofei Yang1, Xia Xu1, Kang Ru1, Xiaoni Deng1, Lifang Hu1, Yu Li1, Songlin Peng2✉, Ge Zhang4✉, Xiao Lin1✉, Airong Qian1✉

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. Department of Spine Surgery, Shenzhen People's Hospital, Southern University of Science and Technology, Jinan University School of Medicine, Shenzhen, 518020, China.
3. Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.
4. 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.
5. Department of Gynaecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
#Co-first authors.

Citation:
Chen Z, Huai Y, Chen G, Liu S, Zhang Y, Li D, Zhao F, Chen X, Mao W, Wang X, Yin C, Yang C, Xu X, Ru K, Deng X, Hu L, Li Y, Peng S, Zhang G, Lin X, Qian A. MiR-138-5p Targets MACF1 to Aggravate Aging-related Bone Loss. Int J Biol Sci 2022; 18(13):4837-4852. doi:10.7150/ijbs.71411. https://www.ijbs.com/v18p4837.htm
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Abstract

Graphic abstract

Senile osteoporosis is one of the major health problems in an aging society. Decreased bone formation due to osteoblast dysfunction may be one of the causes of aging-related bone loss. With increasing evidence suggesting that multiple microRNAs (miRNAs) play important roles in osteoblast function, the relationship between miRNAs and senile osteoporosis has become a popular research topic. Previously, we confirmed that mechanoresponsive miR-138-5p negatively regulated bone anabolic action. In this study, the miR-138-5p level was found to be negatively correlated with BMD and osteogenic markers in bone specimens of senile osteoporotic patients by bioinformatic analysis and experimental verification. Furthermore, high miR-138-5p levels aggravated the decrease of aged osteoblast differentiation in vitro and led to worse bone loss in aged osteoblastic miR-138-5p transgenic mice in vivo. We also previously identified that the target of miR-138-5p, microtubule actin cross-linking factor 1 (MACF1), could attenuate senile osteoporosis. Here, miR-138-5p was demonstrated to regulate aged osteoblast differentiation by targeting MACF1. Finally, the therapeutic inhibition of miR-138-5p counteracted the decrease in bone formation and aging-related bone loss in aged mice. Overall, our results highlight the crucial roles and the molecular mechanism of miR-138-5p in aging-related bone loss and may provide a powerful therapeutic target for ameliorating senile osteoporosis.

Keywords: senile osteoporosis, miR-138-5p, MACF1, osteoblast differentiation, aging-related bone loss


Citation styles

APA
Chen, Z., Huai, Y., Chen, G., Liu, S., Zhang, Y., Li, D., Zhao, F., Chen, X., Mao, W., Wang, X., Yin, C., Yang, C., Xu, X., Ru, K., Deng, X., Hu, L., Li, Y., Peng, S., Zhang, G., Lin, X., Qian, A. (2022). MiR-138-5p Targets MACF1 to Aggravate Aging-related Bone Loss. International Journal of Biological Sciences, 18(13), 4837-4852. https://doi.org/10.7150/ijbs.71411.

ACS
Chen, Z.; Huai, Y.; Chen, G.; Liu, S.; Zhang, Y.; Li, D.; Zhao, F.; Chen, X.; Mao, W.; Wang, X.; Yin, C.; Yang, C.; Xu, X.; Ru, K.; Deng, X.; Hu, L.; Li, Y.; Peng, S.; Zhang, G.; Lin, X.; Qian, A. MiR-138-5p Targets MACF1 to Aggravate Aging-related Bone Loss. Int. J. Biol. Sci. 2022, 18 (13), 4837-4852. DOI: 10.7150/ijbs.71411.

NLM
Chen Z, Huai Y, Chen G, Liu S, Zhang Y, Li D, Zhao F, Chen X, Mao W, Wang X, Yin C, Yang C, Xu X, Ru K, Deng X, Hu L, Li Y, Peng S, Zhang G, Lin X, Qian A. MiR-138-5p Targets MACF1 to Aggravate Aging-related Bone Loss. Int J Biol Sci 2022; 18(13):4837-4852. doi:10.7150/ijbs.71411. https://www.ijbs.com/v18p4837.htm

CSE
Chen Z, Huai Y, Chen G, Liu S, Zhang Y, Li D, Zhao F, Chen X, Mao W, Wang X, Yin C, Yang C, Xu X, Ru K, Deng X, Hu L, Li Y, Peng S, Zhang G, Lin X, Qian A. 2022. MiR-138-5p Targets MACF1 to Aggravate Aging-related Bone Loss. Int J Biol Sci. 18(13):4837-4852.

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