Reference - Detail
| RRC ID | 51898 |
|---|---|
| Author | Moriwaki S, Into T, Suzuki K, Miyauchi M, Takata T, Shibayama K, Niida S. |
| Title | γ-Glutamyltranspeptidase is an endogenous activator of Toll-like receptor 4-mediated osteoclastogenesis. |
| Journal | Sci Rep |
| Abstract |
Chronic inflammation-associated bone destruction, which is observed in rheumatoid arthritis (RA) and periodontitis, is mediated by excessive osteoclastogenesis. We showed previously that γ-glutamyltranspeptidase (GGT), an enzyme involved in glutathione metabolism, acts as an endogenous activator of such pathological osteoclastogenesis, independent of its enzymatic activity. GGT accumulation is clinically observed in the joints of RA patients, and, in animals, the administration of recombinant GGT to the gingival sulcus as an in vivo periodontitis model induces an increase in the number of osteoclasts. However, the underlying mechanisms of this process remain unclear. Here, we report that Toll-like receptor 4 (TLR4) recognizes GGT to activate inflammation-associated osteoclastogenesis. Unlike lipopolysaccharide, GGT is sensitive to proteinase K treatment and insensitive to polymyxin B treatment. TLR4 deficiency abrogates GGT-induced osteoclastogenesis and activation of NF-κB and MAPK signaling in precursor cells. Additionally, GGT does not induce osteoclastogenesis in cells lacking the signaling adaptor MyD88. The administration of GGT to the gingival sulcus induces increased osteoclastogenesis in wild-type mice, but does not induce it in TLR4-deficient mice. Our findings elucidate a novel mechanism of inflammation-associated osteoclastogenesis, which involves TLR4 recognition of GGT and subsequent activation of MyD88-dependent signaling. |
| Volume | 6 |
| Pages | 35930 |
| Published | 2016-10-24 |
| DOI | 10.1038/srep35930 |
| PII | srep35930 |
| PMID | 27775020 |
| PMC | PMC5075938 |
| MeSH | Animals Mice Mice, Knockout Mitogen-Activated Protein Kinases / metabolism Myeloid Differentiation Factor 88 / metabolism* NF-kappa B / metabolism Osteogenesis* Signal Transduction Toll-Like Receptor 4 / deficiency Toll-Like Receptor 4 / metabolism* gamma-Glutamyltransferase / metabolism* |
| IF | 3.998 |
| Times Cited | 5 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | RAW 264(RCB0535) ST2(RCB0224) 293(RCB1637) |