RAGE-dependent NF-kB inflammation processes in the capsule of frozen shoulders

• Published in: Journal of shoulder and elbow surgery 2020-09, Vol.29 (9), p.1884-1891
• Main Authors: Yano, Toshihisa, Hagiwara, Yoshihiro, Ando, Akira, Kanazawa, Kenji, Koide, Masashi, Sekiguchi, Takuya, Itaya, Nobuyuki, Onoki, Takahiro, Suzuki, Kazuaki, Tsuchiya, Masahiro, Sogi, Yasuhito, Yabe, Yutaka, Itoi, Eiji
• Format: Article
• Language: English
• Subjects: Adult; advanced glycation end-products; Aged; Bursitis - metabolism; Case-Control Studies; Female; Frozen shoulder; Gene Expression; high-mobility group box 1; HMGB1 Protein - genetics; HMGB1 Protein - metabolism; Humans; Immunohistochemistry; Ligaments, Articular - metabolism; Male; Middle Aged; NF-kappa B - genetics; NF-kappa B - metabolism; nuclear factor-kappa B; Real-Time Polymerase Chain Reaction; Receptor for Advanced Glycation End Products - genetics; Receptor for Advanced Glycation End Products - metabolism; receptor of advanced glycation end-products; Retrospective Studies; Signal Transduction; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism
• ISSN: 1058-2746; 1532-6500
• DOI: 10.1016/j.jse.2020.01.076

The etiology of frozen shoulder (FS) remains uncertain. Advanced glycation end-products (AGEs) cause the cross-linking and stabilization of collagen and are increased in FS. The purpose of this study was to elucidate the pathogenesis of FS by evaluating the receptor of AGE (RAGE)-dependent pathways. Tissue samples of the coracohumeral ligament (CHL) and anterior inferior glenohumeral ligament (IGHL) were collected from 33 patients with FS, with severe stiffness, and 25 with rotator cuff tears (RCTs) as controls. Gene expression levels of RAGE, high-mobility group box 1 (HMGB1), Toll-like receptor 2 (TLR2), TLR4, nuclear factor-kappa B (NF-kB), and cytokines were evaluated using a quantitative real-time polymerase chain reaction. The immunoreactivities of carboxymethyllysine (CML), pentosidine, and RAGE were also evaluated. CML and pentosidine were further evaluated using high-performance liquid chromatography. Gene expression levels of RAGE, HMGB1, TLR2, TLR4, and NF-kB were significantly greater in the CHLs and IGHLs from the FS group than in those from the RCT group. Immunoreactivities of RAGE and CML were stronger in the CHLs and IGHLs from the FS group than in those from the RCT group. Pentosidine was weakly immunostained in the CHLs and IGHLs from the FS group. CML using high-performance liquid chromatography was significantly greater in the CHLs and IGHLs from the FS group than in those from the RCT group. AGEs and HMGB1 might play important roles in the pathogenesis of FS by binding to RAGE and activating NF-kB signaling pathways. Suppression of these pathways could be a treatment option for FS.