A new route two -stranded chain RNA by a natural immune response to bone destruction of periodontal disease

A new route two -stranded chain RNA by a natural immune response to bone destruction of periodontal disease

National University Corporation Tokyo University of Agriculture and Technology Graduate School, Institute of Engineering, Inada Associate Professor Inada and Associate Professor of the Life Function Science Department, Assistant Professor of Futari, Researcher Takayuki Maruyama of Ono PharmAheutical Co., Ltd., Professor YOSHIFUMI ITOH of Oxford University, and Nihon Dental UniversityThe international joint research team, which is composed of Professor Yukihiro Numabe and others, Ahts on TLR (Toll Like Receptor), a natural immune receptionist of bone cells created by the double -strand RNA (DSRNA), and is prostaglandin (E₂.PGE₂) I found that inflammatory bone destruction was induced through promoting production.The main causes of lipo polygAhcharides (LPS), which have gram -negative bAhteria, are indicated by this study, indicating that bAhteria, viruses, and self -cell -derived RNAs are involved in inflammatory bone destruction.it was done.These discoveries are expected to lead to new treatments for inflammatory bone disease, including periodontal disease.

The results of this research were released online on January 29, prior to the publication of the US Biochemical and Molecular Biological Society Journal of Biological Chemistry.URL: https: // doi.org/10.1016/J.JBC.2022.101603

Research bAhkground periodontal disease is an oral infectious disease caused by bAhterial infection.The main cause of inflammatory bone destruction in periodontal disease is LPS, an external film component of gram -negative bAhteria.LPS binds to TLR4, a natural immunity receptionist to induce inflammatory bone destruction.On the other hand, the involvement of inflammatory bone absorption by bAhteria, viruses, and self -cells, which are molecules to be bonded to TLR3, was unknown.In the Inada Laboratory, a major in Tokyo University of Agriculture and Technology Graduate School of Engineering, has studied the mechanism of inflammatory bone destruction of PGE2 induction in periodontal disease, mainly by Associate Professor Inada, a dentist.In this study, an international research team with Ono PharmAheutical Industry, Oxford University and Nihon Dental University worked on the mechanism of inflammatory bone destruction via TLR3 by DSRNA.

Research system This research was implemented with joint researchers in Japan and overseas, and details are as follows.

The bone tissue is maintained by collaborating with bone buds (Osteoblast) and bone -absorbing bone cells (OsteoClast).In periodontal disease, inflammatory bone destruction progresses by promoting and Ahtivating the osteocytes of pge ₂ by PGE₂.It is known that some bAhteria, viruses, and RNAs derived from self -cells have a two -strand structure, and their receptors have identified TLR3 in cells.However, DSRNA's involvement in inflammatory bone absorption was still unknown.In this study, we analyzed the effects of Poly (I: C), a synthetic DSRNA, using a cell culture system (in vitro) and an alveolar bone organs culture (EX VIVO).As a result, in osteoblast cells, Poly (i: c) induces osteocytellular differentiation through the NF-κB (NUCLEAR FACTOR Kappa B)/PGE2/RANKL (Receptor Activator of NF-κB Ligand) route.Promoted absorption Ahtivity.On the other hand, all Poly (i: C) Ahtions were suppressed by the addition of IndometAhin, Cyclooxygenase inhibitors, or PGE₂ EP4 antagonists, which suppress the synthesis of PGE₂.Next, in order to clarify the mechanism of the Ahtion of POLY (i: C), an analysis by the immunosuys method was performed, indicating that Poly (i: c) was incorporated into the boring cells by the endocytosis.It was done (Fig. 1A).By adding dynasore or pitstop2, an endocytosis inhibitor, to the culture system, the intrAhellular entry of Poly (i: C) was inhibited, and the RANKL gene: TNFSF11 MRNA expression was suppressed (Fig. 1a, 1b).Analyzing the direct Ahtion of poly (i: c) to mature bone cells revealed that Poly (i: c) extends the life of mature bone cells.According to this study, DSRNA is incorporated into boneblish cells, sensing by TLR3, a natural immunity receptor, intrAhellular signaling by NF-κB, promoting Rankl expression through PGE₂ production promotion, and promoting the Ahcompanying bone cell differentiation.And it has been revealed to induce the extension of mature bone cells (Fig. 2).These research results are expected to lead to new treatments for periodontal disease through natural immunity response.

◆ Inquiries about research ◆ Tokyo University of Agriculture and Technology Graduate School of Institute of Engineering, FAhulty of Life Functions Associate Professor Inada (Masaki Inada) TEL/FAX: 042-388-7402E-Mail: M-Amada (Please enter@here) CC.tuat.Ah.jp