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The pivotal role of microRNA-21 in osteoclastogenesis inhibition by anthracycline glycoside aloin

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Abstract

Osteopenic disorders such as osteoporosis and rheumatoid arthritis are characterized by excessive bone resorption by osteoclasts relative to bone formation by osteoblasts. MicroRNAs are emerging as key players in bone remodeling, modulating the functions of both osteoblasts and osteoclasts. Among them, miR-21 is highly expressed in osteoclast precursors and is known to regulate genesis, differentiation, and apoptosis of osteoclasts. The pro-osteoclastogenic nature of miR-21 makes it a potential candidate as a therapeutic target to treat bone disorders. We had previously demonstrated that anthroglycoside aloin derived from Aloe vera was effective in promoting osteoblastogenesis and inhibiting osteoclastogenesis. The present study investigated the role of miR-21 in aloin’s inhibitory effect on osteoclast differentiation. Aloin effectively suppressed receptor activator of nuclear factor kappa-B (NFĸB) ligand (RankL)-induced miR-21 expression via repression of NFĸB activation. MiR-21 suppression resulted in upregulation of osteoclast suppressor programmed cell death protein 4 (PDCD4), and downregulation of osteoclast marker cathepsin K. Knockdown or gain-of-function studies revealed that miR-21 was pivotal to aloin’s inhibitory effect on osteoclastogenesis. This study also highlights the dynamic potential of aloin as a therapeutic agent to treat osteopenic disorders.

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Acknowledgements

This study was supported by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan to M.R.

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Authors and Affiliations

  1. Department of Applied Physiology, Faculty of Medicine, University of Miyazaki, Miyazaki, 889-1692, Japan

    Radha Madhyastha, Harishkumar Madhyastha, Queen Intan Nurrahmah, Yuichi Nakajima & Masugi Maruyama

  2. Faculty of Medical Technology, Prince of Songkla University, Hatyai, Songkla, 90110, Thailand

    Yutthana Pengjam

Authors
  1. Radha Madhyastha
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  2. Harishkumar Madhyastha
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  3. Yutthana Pengjam
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  4. Queen Intan Nurrahmah
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  5. Yuichi Nakajima
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  6. Masugi Maruyama
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Correspondence to Radha Madhyastha.

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Madhyastha, R., Madhyastha, H., Pengjam, Y. et al. The pivotal role of microRNA-21 in osteoclastogenesis inhibition by anthracycline glycoside aloin. J Nat Med 73, 59–66 (2019). https://doi.org/10.1007/s11418-018-1237-3

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  • DOI: https://doi.org/10.1007/s11418-018-1237-3

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