Potential enhancement of osteoclastogenesis by severe acute respiratory syndrome coronavirus 3a/X1 protein

Saemi Obitsu, Nursarat Ahmed, Hironori Nishitsuji, Atsuhiko Hasegawa, Ken ichi Nakahama, Ikuo Morita, Kazuo Nishigaki, Takaya Hayashi, Takao Masuda, Mari Kannagi

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7 Citations (Scopus)

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) causes a lung disease with high mortality. In addition, osteonecrosis and bone abnormalities with reduced bone density have been observed in patients following recovery from SARS, which were partly but not entirely explained by the short-term use of steroids. Here, we demonstrate that human monocytes, potential precursors of osteoclasts, partly express angiotensin converting enzyme 2 (ACE2), a cellular receptor of SARS-CoV, and that expression of an accessory protein of SARS-CoV, 3a/X1, in murine macrophage cell line RAW264.7 cells, enhanced NF-κB activity and differentiation into osteoclast-like cells in the presence of receptor activator of NF-κB ligand (RANKL). Furthermore, human epithelial A549 cells expressed ACE2, and expression of 3a/X1 in these cells up-regulated TNF-α, which is known to accelerate osteoclastogenesis. 3a/X1 also enhanced RANKL expression in mouse stromal ST2 cells. These findings indicate that SARS-CoV 3a/X1 might promote osteoclastogenesis by direct and indirect mechanisms.

Original languageEnglish
Pages (from-to)1457-1464
Number of pages8
JournalArchives of Virology
Volume154
Issue number9
DOIs
Publication statusPublished - 01-09-2009

All Science Journal Classification (ASJC) codes

  • Virology

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    Obitsu, S., Ahmed, N., Nishitsuji, H., Hasegawa, A., Nakahama, K. I., Morita, I., Nishigaki, K., Hayashi, T., Masuda, T., & Kannagi, M. (2009). Potential enhancement of osteoclastogenesis by severe acute respiratory syndrome coronavirus 3a/X1 protein. Archives of Virology, 154(9), 1457-1464. https://doi.org/10.1007/s00705-009-0472-z