Potential enhancement of osteoclastogenesis by severe acute respiratory syndrome coronavirus 3a/X1 protein.
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-kappaB activity and differentiation into osteoclast-like cells in the presence of receptor activator of NF-kappaB ligand (RANKL). Furthermore, human epithelial A549 cells expressed ACE2, and expression of 3a/X1 in these cells up-regulated TNF-alpha, 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.
Obitsu
Saemi
S
Department of Immunotherapeutics, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Ahmed
Nursarat
N
Nishitsuji
Hironori
H
Hasegawa
Atsuhiko
A
Nakahama
Ken-ichi
K
Morita
Ikuo
I
Nishigaki
Kazuo
K
Hayashi
Takaya
T
Masuda
Takao
T
Kannagi
Mari
M
D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001862:Bone Resorption / Q000821:virology*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus; D045169:Severe Acute Respiratory Syndrome / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D017154:Stromal Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D015678:Viral Structural Proteins / Q000378:metabolism*; D000086082:Viroporin Proteins
D000085962:Angiotensin-Converting Enzyme 2; D007703:Peptidyl-Dipeptidase A; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D015678:Viral Structural Proteins; C515313:ORF3A protein, SARS coronavirus; D000086082:Viroporin Proteins; C505689:Tnfsf11 protein, mouse; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse
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