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        Angiopoietin-Like Protein 2 Induces Synovial Inflammation in the Facet Joint Leading to Degenerative Changes via Interleukin-6 Secretion

        Kazuki Sugimoto,Takayuki Nakamura,Takuya Tokunaga,Yusuke Uehara,Tatsuya Okada,Takuya Taniwaki,Toru Fujimoto,Yuichi Oike,Eiichi Nakamura 대한척추외과학회 2019 Asian Spine Journal Vol.13 No.3

        Study Design: Experimental human study. Purpose: To determine whether angiopoietin-like protein 2 (ANGPTL2) is highly expressed in the hyperplastic facet joint (FJ) synovium and whether it activates interleukin-6 (IL-6) secretion in FJ synoviocytes. Overview of Literature: Mechanical stress-induced synovitis is partially, but significantly, responsible for degenerative and subsequently osteoarthritic changes in the FJ tissues in patients with lumbar spinal stenosis (LSS). However, the underlying molecular mechanism remains unclear. IL-6 is highly expressed in degenerative FJ synovial tissue and is responsible for local chronic inflammation. ANGPTL2, an inflammatory and mechanically induced mediator, promotes the expression of IL-6 in many cells. Methods: FJ tissues were harvested from five patients who had undergone lumbar surgery. Immunohistochemistry for ANGPTL2, IL-6, and cell markers was performed in the FJ tissue samples. After cultured synoviocytes from the FJ tissues were subjected to mechanical stress, ANGPTL2 expression and secretion were measured quantitatively using real-time quantitative reverse-transcription–polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. Following ANGPTL2 administration in the FJ synoviocytes, anti-nuclear factor-κB (NF-κB) activation was investigated using immunocytochemistry, and IL-6 expression and secretion were assayed quantitatively with or without NF-κB inhibitor. Moreover, we assessed whether ANGPTL2-induced IL-6 modulates leucocyte recruitment in the degenerative process by focusing on the monocyte chemoattractant protein-1 (MCP-1) expression. Results: ANGPTL2 and IL-6 were highly expressed in the hyperplastic FJ synovium samples. ANGPTL2 was co-expressed in both, fibroblast-like and macrophage-like synoviocytes. Further, the expression and secretion of ANGPTL2 in the FJ synoviocytes increased in response to stimulation by mechanical stretching. ANGPTL2 protein promoted the nuclear translocation of NF-κB and induced IL-6 expression and secretion in the FJ synoviocytes. This effect was reversed following treatment with NF-κB inhibitor. Furthermore, ANGPTL2-induced IL-6 upregulated the MCP-1 expression in the FJ synoviocytes. Conclusions: Mechanical stress-induced ANGPTL2 promotes chronic inflammation in the FJ synovium by activating IL-6 secretion, leading to FJ degeneration and subsequent LSS.

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        Characterization of Elemental Composition and Valence State of Cyclone-collected Aerosol Particles Using EDXRF and XAFS at Three Sites in Japan

        Tomoaki Okuda,Weidong Jing,Katsutomo Saito,Takuma Okamoto,Hibiki Saito,Kazuki Sugimoto,Chiharu Nishita-Hara,Keiichiro Hara,Masahiko Hayashi,Shuichi Hasegawa 한국대기환경학회 2022 Asian Journal of Atmospheric Environment (AJAE) Vol.16 No.2

        The valence state and concentration of metallic pollutants are important factors contributing to the health effects of respirable particulate matter (PM); however, they have not been well studied. In this study, coarse and fine powder samples of atmospheric PM were collected using a cyclone system at Kanagawa (KO), Saitama (SA), and Fukuoka (FU) in Japan in 2017. Energy dispersive X-ray fluorescence spectroscopy (EDXRF) was used to measure the concentrations of nine metallic elements (Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, and Pb), and X-ray absorption fine structure (XAFS) spectroscopy was used to analyze the valence states of target elements (Cr, Mn, Fe, Cu, and Zn). The EDXRF results indicated that the average contents of Fe, Ti, and Zn were much higher than those of the other six elements in all samples. The XAFS results showed that the major valence states of the elements were Cr(III), Mn(II), Fe(III), Cu(II), and Zn(II). The percentages of Mn(IV), Fe(II), and Cu(0) were higher in KO and SA samples than in FU samples. Mn(0) and Zn(0) were detected in some samples only, and Cu(I) was not detected in any samples. Correlation analysis, principal component analysis, and cluster analysis were performed on the EDXRF and XAFS data of the target elements. The source identification results showed that the sources of metal contaminants in the samples varied considerably between sampling sites and depended on the industrial structure and geographical location of the sampling area. Our findings on the different valence states of the elements may be important for determining the toxicity of PM at different locations.

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