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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
['Yano|Toshihisa|T|', 'Hagiwara|Yoshihiro|Y|', 'Ando|Akira|A|', 'Kanazawa|Kenji|K|', 'Koide|Masashi|M|', 'Sekiguchi|Takuya|T|', 'Itaya|Nobuyuki|N|', 'Onoki|Takahiro|T|', 'Suzuki|Kazuaki|K|', 'Tsuchiya|Masahiro|M|', 'Sogi|Yasuhito|Y|', 'Yabe|Yutaka|Y|', 'Itoi|Eiji|E|']
D000328:Adult D000368:Aged D002062:Bursitis D016022:Case-Control Studies D005260:Female D015870:Gene Expression D024243:HMGB1 Protein D006801:Humans D007150:Immunohistochemistry D008023:Ligaments, Articular D008297:Male D008875:Middle Aged D016328:NF-kappa B D060888:Real-Time Polymerase Chain Reaction D000067759:Receptor for Advanced Glycation End Products D012189:Retrospective Studies D015398:Signal Transduction D051195:Toll-Like Receptor 2 D051197:Toll-Like Receptor 4
Frozen shoulder advanced glycation end-products gene expression high-mobility group box 1 nuclear factor-kappa B receptor of advanced glycation end-products