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. 2022 Mar 22;23(1):271.
doi: 10.1186/s12891-022-05229-5.

Advanced glycation end products are associated with limited range of motion of the shoulder joint in patients with rotator cuff tears associated with diabetes mellitus

Issei Shinohara  1 , Yutaka Mifune  2 , Atsuyuki Inui  1 , Hanako Nishimoto  1 , Kohei Yamaura  1 , Shintaro Mukohara  1 , Tomoya Yoshikawa  1 , Tatsuo Kato  1 , Takahiro Furukawa  1 , Yuichi Hoshino  1 , Takehiko Matsushita  1 , Ryosuke Kuroda  1
Affiliations

Advanced glycation end products are associated with limited range of motion of the shoulder joint in patients with rotator cuff tears associated with diabetes mellitus

Issei Shinohara et al. BMC Musculoskelet Disord. .

Abstract

Background: Most degenerative rotator cuff tears (RCTs) are associated with a limited range of motion (ROM) of the shoulder joint. Additionally, patients with diabetes mellitus (DM) show a higher frequency of limited ROM. Recently, advanced glycation end products (AGEs) of proteins have been observed to cause tissue fibrosis, primarily through abnormal collagen cross-linking and oxidative stress. In this study, we investigated the effect of AGEs on ROM limitation in the shoulder capsule and its relationship with DM in the patients with RCTs.

Methods: Sixteen patients (eight in the DM and non-DM groups) who underwent arthroscopic surgery for RCT with limited shoulder ROM were included in this study. AGE-related pathologies in both groups were compared, and the relationship between AGE accumulation and shoulder joint ROM was evaluated. Shoulder capsule tissue was harvested and subjected to histological and in vitro evaluation.

Results: The DM group displayed high levels of AGEs and reactive oxygen species (ROS), and reduced cell viability. There was a significant positive correlation between ROS expression, apoptosis, and preoperative hemoglobin A1c. ROS expression, apoptosis, and ROM of the shoulder joint showed a negative correlation. The NADPH oxidase (NOX) expression and collagen III/I ratio were significantly higher in the DM group than in the non-DM group.

Conclusions: The DM group showed significant AGEs deposition in the shoulder capsule. Additionally, there was a significant association between AGEs and ROM limitation. Collectively, the findings suggest that the oxidative stress induced by AGEs deposition, which leads to fibrosis and local inflammation, might contribute to the limited ROM of the shoulder joint in patients with RCTs accompanied by DM.

Keywords: Advanced glycation end products; Cell viability; Range of motion; Reactive oxygen species; Rotator cuff tears; Shoulder capsule.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Hematoxylin and eosin (H&E) staining of the shoulder capsule cells shows dense fibroblasts and disorganized collagen arrangement in the DM group
Fig. 2
Fig. 2
Immunostaining for advanced glycation end products (AGEs) and receptor of AGEs (RAGE). a Quantification of the percentage of immunostaining to H&E staining using ImageJ. b Both AGEs and RAGE staining were significantly higher in the DM group (p < 0.05) than in the control group
Fig. 3
Fig. 3
Viability of the shoulder capsule cells. a Cell viability was significantly lower in the DM group compared with that in the control group (p = 0.002). b There was a significant positive correlation between cell viability and shoulder joint ROM (p < 0.01)
Fig. 4
Fig. 4
ROS staining of the shoulder capsule cells. a The percentage of ROS staining was significantly higher in the DM group (p = 0.003). b The percentage of ROS staining showed significant positive correlation with preoperative HbA1c (p < 0.01) and a significant negative correlation with the preoperative ROM of the shoulder joint (p < 0.01)
Fig. 5
Fig. 5
Apoptosis rate. a) The percentage of apoptosis was significantly higher in the DM group (p = 0.006). b) The percentage of apoptosis showed a significant positive correlation with preoperative HbA1c (p < 0.01) and a significant negative correlation with the preoperative ROM of the shoulder joint (p < 0.01)
Fig. 6
Fig. 6
Results from real-time PCR
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