Eur Rev Med Pharmacol Sci 2019; 23 (11): 4530-4540

DOI: 10.26355/eurrev_201906_18028

β4GalT1 promotes inflammation in human osteoarthritic fibroblast-like synoviocytes by enhancing autocrine TNF-α activity

D.-W. Xu, X.-H. Zhu, M.-Q. He, Q. Yuan, Q.-R. Dong

Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China. dongqirongdoctor@163.com


OBJECTIVE: Synovial inflammation plays an important role in the pathogenesis of osteoarthritis (OA), and β4GalT1 has been reported to be involved in the inflammatory process. The aim of our study was to investigate the role of β4GalT1 in the progression of inflammation and analyze the association between β4GalT1 and tumor necrosis factor (TNF)-α in human OA fibroblast-like synoviocytes (FLS).

PATIENTS AND METHODS: Primary cultured FLS isolated from OA synovial tissues were cultured, and the levels of β4GalT1, TNF-α, MMP-3, p/t-ERK, p/t-JNK, and p/t-P38 were analyzed by Western blotting. An enzyme-linked immunosorbent assay (ELISA) was performed to measure the secretion of TNF-α, interleukin (IL)-1β, and IL-6 in OA-FLS. Immunofluorescence staining was used to examine the co-localization of β4GalT1 and TNF-α or THY1. RT-PCR was used to detect the transfection efficiency of β4GalT1.

RESULTS: The expression of β4GalT1 was increased in OA-FLS. β4GalT1 promoted cell invasion, MMP-3 production, and the secretion of TNF-α, IL-1β, and IL-6. si-TNF-α attenuated the β4GalT1-enhanced cell invasion and inflammatory factor secretion in OA-FLS. Furthermore, β4GalT1 increased autocrine TNF-α signaling in OA-FLS. β4GalT1 knockdown successfully decreased autocrine TNF-α activity, while β4GalT1 overexpression increased autocrine TNF-α activity in OA-FLS. Moreover, β4GalT1 enhanced the ERK, JNK, and P38 MAPK signaling pathways through the induction of autocrine TNF-α signaling in OA-FLS.

CONCLUSIONS: β4GalT1 may promote the inflammatory progression of OA-FLS by enhancing autocrine TNF-α signaling.

To cite this article

D.-W. Xu, X.-H. Zhu, M.-Q. He, Q. Yuan, Q.-R. Dong
β4GalT1 promotes inflammation in human osteoarthritic fibroblast-like synoviocytes by enhancing autocrine TNF-α activity

Eur Rev Med Pharmacol Sci
Year: 2019
Vol. 23 - N. 11
Pages: 4530-4540
DOI: 10.26355/eurrev_201906_18028