Mechanical strain regulates osteoclastogenesis via modulating the PTEN/PI3K/Akt signal pathway through miR-21 View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2021-11-22

AUTHORS

Bin Fang, Kailong Zhang, Jie Zhang, Zhenda Chen, Yunxin Xuan, Hongbin Huang

ABSTRACT

Mechanical strain regulated osteoclastic differentiation and angiogenesis are crucial for bone modeling and remodeling, and previous data indicate that high-magnitude strain within physiological load regulates osteoclastic differentiation. However, the underlying mechanisms are still not fully understood. In the present study, the RAW264.7 mouse monocyte/macrophage was used as an osteoclast precursor, and the bone marrow-derived macrophages (BMMs) were isolated and cultured in vitro. The above cells were subjected to macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL) for the induction of osteoclast differentiation. Subsequently, the above cells were stretched by differential strain magnitudes to simulate the mechanical stimuli in the physiological conditions, and we found that low-magnitude strain (100 με) increased the expression levels of Acp5, Clcn7, MMP9 and Ctsk to promote osteoclastogenesis, while high-magnitude strain (3000 με) had opposite effects. In addition, we noticed that high-magnitude strain upregulated PTEN to inactivate the PI3K/Akt signaling pathway, and silencing of PTEN abrogated the suppressing effects of high-magnitude strain on osteoclastic differentiation. Next, we screened out that high-magnitude strain downregulated miR-21 to promote PTEN expressions in a competing endogenous RNA (ceRNA)-dependent manner. Finally, upregulation of miR-21 recovered osteoclastic differentiation in RAW264.7 and BMMs cells stimulated with high-magnitude strain. Collectively, our findings suggested that high-magnitude mechanical strain affected osteoclastic differentiation through modulating the miR-21/PTEN/PI3K/Akt signaling cascade, which provided potential strategies for the treatment of bone-related diseases. More... »

PAGES

1-11

References to SciGraph publications

  • 2019-02-22. miRNA-21 promotes osteogenesis via the PTEN/PI3K/Akt/HIF-1α pathway and enhances bone regeneration in critical size defects in STEM CELL RESEARCH & THERAPY
  • 2019-08-08. MiR-135-5p promotes osteoblast differentiation by targeting HIF1AN in MC3T3-E1 cells in CELLULAR & MOLECULAR BIOLOGY LETTERS
  • 2020-07-17. Osteocyte-derived exosomes induced by mechanical strain promote human periodontal ligament stem cell proliferation and osteogenic differentiation via the miR-181b-5p/PTEN/AKT signaling pathway in STEM CELL RESEARCH & THERAPY
  • 2018-08-27. Rehmanniae Radix Preparata suppresses bone loss and increases bone strength through interfering with canonical Wnt/β-catenin signaling pathway in OVX rats in OSTEOPOROSIS INTERNATIONAL
  • 2020-08-24. miRNA-425-5p enhances lung cancer growth via the PTEN/PI3K/AKT signaling axis in BMC PULMONARY MEDICINE
  • 2019-04-25. miR-363-3p is activated by MYB and regulates osteoporosis pathogenesis via PTEN/PI3K/AKT signaling pathway in IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY - ANIMAL
  • 2019-02-08. Systematic Review of miRNA as Biomarkers in Alzheimer’s Disease in MOLECULAR NEUROBIOLOGY
  • 2020-01-15. Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk in NATURE COMMUNICATIONS
  • 2020-04-06. miR-140-3p aggregates osteoporosis by targeting PTEN and activating PTEN/PI3K/AKT signaling pathway in HUMAN CELL
  • 2019-03-21. miR-142-5p promotes the osteoclast differentiation of bone marrow-derived macrophages via PTEN/PI3K/AKT/FoxO1 pathway in JOURNAL OF BONE AND MINERAL METABOLISM
  • 2017-02-27. miR-21 deficiency inhibits osteoclast function and prevents bone loss in mice in SCIENTIFIC REPORTS
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