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

Zhihao Chen, Ying Huai, Gaoyang Chen, Shuyu Liu, Yan Zhang, Dijie Li, Fan Zhao, Xiaofeng Chen, Wenjing Mao, Xuehao Wang, Chong Yin, Chaofei Yang, Xia Xu, Kang Ru, Xiaoni Deng, Lifang Hu, Yu Li, Songlin Peng*, Ge Zhang*, Xiao Lin*Airong Qian*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4837-4852
Number of pages16
JournalInternational Journal of Biological Sciences
Volume18
Issue number13
DOIs
Publication statusPublished - 18 Jul 2022

Scopus Subject Areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

User-Defined Keywords

  • senile osteoporosis
  • miR-138-5p
  • MACF1
  • osteoblast differentiation
  • aging-related bone loss

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