RT Journal Article
SR Electronic
T1 The level of synovial human VEGFA, IL-8 and MIP-1α correlate with truncation of lubricin glycans in osteoarthritis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.11.434779
DO 10.1101/2021.03.11.434779
A1 Shan Huang
A1 Kristina A. Thomsson
A1 Chunsheng Jin
A1 Henrik Ryberg
A1 Nabangshu Das
A1 André Struglics
A1 Ola Rolfson
A1 Lena I Björkman
A1 Thomas Eisler
A1 Tannin A. Schmidt
A1 Gregory D. Jay
A1 Roman Krawetz
A1 Niclas G. Karlsson
YR 2021
UL http://biorxiv.org/content/early/2021/03/30/2021.03.11.434779.abstract
AB Osteoarthrithis (OA) is an endemic disease due to the increase of the world’s elderly population. Previously thought to be a consequence of an imbalance between cartilage degradation and biosynthesis, it is now recognized as a disease also involving inflammation, hence influencing the level of inflammatory cytokines, growth factors and chemokines. Lubricin is a mucin type molecule where its OA induced glycosylation truncation propels a deteriorating lubrication of the articular cartilage. The objective of this study was to explore the OA driven truncation of O-linked glycosylation of synovial lubricin and its cross talk with systemic and local (synovial fluid, SF) inflammation. We compared the systemic level of cytokines/chemokine in OA patients’ and controls’ plasma with their local level in SF using a 44 plex screen. The level of 27 cytokines and chemokines was consistently measured in both plasma and SF. The data showed that the levels of cytokines and chemokines in OA plasma display limited correlation to their counterpart in SF. The level of synovial IL-8 and MIP-1α and VEGFA in OA patients, but not their plasma level, where the only cytokines that displayed a significant correlation to the observed lubricin O-linked glycosylation truncation. These cytokines were also shown to be upregulated exposing fibroblast like synoviocytes from healthy and OA patients to recombinant lubricin with truncated glycans mainly consisting of Tn-antigens, while lubricin with sialylated and non-sialylated T anigens did not have any effect. The data suggest that truncated glycans of lubricin, as found in OA, promotes the synovial cytokine production and exerebate the local synovial inflammation.Competing Interest StatementGJ, RK and TS authored patents related to rhPRG4 and and GDJ and TS hold equity in Lubris BioPharma LLC. TS is also a paid consultant for Lubris BioPharma, LLC. NGK, SH and CJ authored a patent using lubricin and cytokines for diagnostics and NGK and CJ hold equity in Lynxon AB. KAT, HR, AS, ND, OR, LIB and TE declare no conflict of interest.