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

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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.

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All the involved data had been included in the manuscript, and the original raw data could be obtained from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Spine Surgery, The Central Hospital Affiliated to Shaoxing University, No. 1 Huayu Road, Keqiao District, Shaoxing City, 312030, Zhejiang Province, China

    Bin Fang

  2. Beijing Zhongwei Research Center of biological and translational medicine, Beijing, China

    Kailong Zhang, Jie Zhang, Zhenda Chen & Yunxin Xuan

  3. Department of Orthopedics, Yiwu Central Hospital, No. 519 Nan Men Street, Yiwu City, 322000, Zhejiang Province, China

    Hongbin Huang

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  1. Bin Fang
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  4. Zhenda Chen
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  5. Yunxin Xuan
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Fang, B., Zhang, K., Zhang, J. et al. Mechanical strain regulates osteoclastogenesis via modulating the PTEN/PI3K/Akt signal pathway through miR-21. Cytotechnology 74, 65–75 (2022). https://doi.org/10.1007/s10616-021-00507-x

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