Molecular analysis of RANKL-independent cell fusion of osteoclast-like cells Induced by TNF-α, lipopolysaccharide, or peptidoglycan

Hotokezaka, Hitoshi, Sakai, Eiko, Ohara, Naoya, Hotokezaka, Yuka, Gonzales, Carmen, Matsuo, Ken-ichiro, Fujimura, Yuji, Yoshida, Noriaki, and Nakayama, Koji (2007) Molecular analysis of RANKL-independent cell fusion of osteoclast-like cells Induced by TNF-α, lipopolysaccharide, or peptidoglycan. Journal of Cellular Biochemistry, 101 (1). pp. 122-134.

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Focusing on the final step of osteoclastogenesis,we studied cell fusion from tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells into multinuclear cells. TRAP-positive mononuclear cells before generation of multinuclear cells by cell fusion were differentiated from RAW264.7 cells by treatment with receptor activator of nuclear factor kappa B ligand (RANKL), and then the cells were treated with lipopolysaccharide (LPS), followed by culturing for further 12 h. LPS-induced cell fusion even in the absence of RANKL. Similarly, tumor necrosis factor (TNF)-α and peptidoglycan (PGN) induced cell fusion, but M-CSF did not. The cell fusion induced by RANKL, TNF-α, and LPS was specifically blocked by osteoprotegerin (OPG), anti-TNF-α antibody, and polymyxin B, respectively. LPS- and PGN-induced cell fusion was partly inhibited by anti-TNF-α antibody but not by OPG.When TRAP-positive mononuclear cells fused to yield multinuclear cells, phosphorylation of Akt, Src, extracellular signal-regulated kinase (ERK), p38MAPK (p38), and c-JunNH2-terminal kinase (JNK) was observed. The specific chemical inhibitors LY294002 (PI3K), PP2 (Src), U0126 (MAPK-ERK kinase (MEK)/ERK), and SP600125 (JNK) effectively suppressed cell fusion, although SB203580 (p38) did not. mRNA of nuclear factor of activated T-cells c1 (NFATc1) and dendritic cell-specific transmembrane protein (DC-STAMP) during the cell fusion was quantified, however, there wasno obvious difference among the TRAP-positive mononuclear cells treated with or without M-CSF,RANKL, TNF-α, LPS, or GN. Collectively, RANKL,TNF-α, LPS, and PGN induced cell fusion of osteoclasts through their own receptors. Subsequent activation of signaling pathways involving PI3K, Src, ERK, and JNK molecules was required for the cell fusion. Although DC-STAMP is considered to be a requisite for cell fusion of osteoclasts, cell fusion-inducing factors other than DC-STAMP might be necessary for the cell fusion.

Item ID: 45162
Item Type: Article (Research - C1)
ISSN: 1097-4644
Keywords: TNF-α; lipopolysaccharide; peptidoglycan; cell fusion; osteoclasts
Funders: Ministry of Education, Science, Sport and Culture, Japan (MESSC)
Projects and Grants: MESSC #15592169, MESSC #DC2-16-6032
Date Deposited: 14 Sep 2016 01:13
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1105 Dentistry > 110506 Orthodontics and Dentofacial Orthopaedics @ 90%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060111 Signal Transduction @ 10%
SEO Codes: 92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920402 Dental Health @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920113 Oro-Dental Disorders @ 50%
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