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Mycoepoxydiene suppresses RANKL-induced osteoclast differentiation and reduces ovariectomy-induced bone loss in mice

  • Applied microbial and cell physiology
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Abstract

Mycoepoxydiene (MED) is a compound isolated from the marine fungal Diaporthe sp. HLY-1 associated with mangroves. MED has various biological effects such as anti-microbial, anti-cancer, and anti-inflammatory activities. However, the effect of MED on the differentiation of osteoclasts, the multinucleated bone-resorbing cells which play a crucial role in bone remodeling, is still unknown. In this study, we showed that MED could inhibit receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation and the expression of three well-known osteoclast markers such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K in bone marrow-derived macrophages. Furthermore, we found that MED inhibited the expression of nuclear factor of activated T cells c1, a key transcriptional factor in osteoclast differentiation, via inhibiting the phosphorylation of TAK1 and then blocking the activation of NF-κB and ERK1/2 pathways. Moreover, MED could prevent bone loss in ovariectomized mice. Taken together, we demonstrate for the first time that MED can suppress RANKL-induced osteoclast differentiation in vitro and ovariectomy-induced osteoporosis in vivo, suggesting that MED is a potential lead compound for the development of novel drugs for osteoporosis treatment.

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Acknowledgments

This work was supported by grants from the National Basic Research Program of China (973 Program, 2009CB522200 and 2010CB833802), the Natural Science Foundation of Fujian Province of China (2010 J06014), the Program for New Century Excellent Talents in University of the Ministry of Education (NCET-10-0718), and the Natural Science Foundation of China (30770455 and 31170819).

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The authors disclose no conflict of interest.

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Authors and Affiliations

  1. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China

    Jingwei Zhu, Qiang Chen, Xiaochun Xia, Pingli Mo & Chundong Yu

  2. School of Pharmaceutical Sciences, Shandong University, Jinan, China

    Yuemao Shen

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  1. Jingwei Zhu
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  2. Qiang Chen
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  3. Xiaochun Xia
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  4. Pingli Mo
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Correspondence to Yuemao Shen or Chundong Yu.

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Zhu, J., Chen, Q., Xia, X. et al. Mycoepoxydiene suppresses RANKL-induced osteoclast differentiation and reduces ovariectomy-induced bone loss in mice. Appl Microbiol Biotechnol 97, 767–774 (2013). https://doi.org/10.1007/s00253-012-4146-5

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