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

Zhihao Chen, Fan Zhao, Chao LIANG, Lifang Hu, Dijie Li, Yan Zhang, Chong Yin, Lei Chen, Luyao Wang, Xiao Lin, Peihong Su, Jianhua Ma, Chaofei Yang, Ye Tian, Wenjuan Zhang, Yu Li, Songlin Peng, Weiyi Chen, Ge ZHANG, Airong Qian*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)12263-12278
Number of pages16
JournalTheranostics
Volume10
Issue number26
DOIs
Publication statusPublished - 2020

Scopus Subject Areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

User-Defined Keywords

  • Bone formation
  • Mechanoresponsive
  • MiR-138-5p
  • Osteoporosis
  • Sensitize

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