Effect of isolated hyperglycemia on native mechanical and biologic shoulder joint properties in a rat model

Abstract

Recently, diabetes has been linked to rotator cuff disease and adhesive capsulitis, conditions with increased stiffness and inflammation. Unfortunately, limited research exists examining how hyperglycemia affects the native shoulder (tendon and capsule) properties. Therefore, the objectives of this study were to compare shoulder joint mechanics, tendon properties (mechanics and immunohistochemistry), and capsule of healthy control and hyperglycemic rats 8 weeks following induction of hyperglycemia with a submaximal dose of streptozotocin (STZ). Eighteen rats were injected with STZ to induce hyperglycemia or citrate buffer (control) and underwent normal cage activity for 8 weeks. Passive joint mechanics demonstrated significantly less external rotation in the hyperglycemic group compared to controls, with no other group differences. Tendon mechanical properties (stiffness and modulus) were not significantly different between groups at both the insertion site and mid-substance. Immunohistochemistry staining of the tendon and capsule demonstrated significantly increased interleukin 1-beta (IL1-β) and advanced glycated end-products (AGE) staining localized to the insertion and mid-substance of the tendon but not the capsule. In addition, tumor necrosis factor alpha (TNF-α) staining was significantly increased in the superior capsule but not the supraspinatus tendon. This study demonstrates that isolated hypergylcemia does not diminish shoulder mechanical properties but does induce a chronic inflammatory response.

Keywords: capsule; hyperglycemia; rat model; rotator cuff; tendon.

Figure 1

A representative histology image of the whole shoulder stained with H&E.

Figure 2

(A) Fasting blood glucose and (B) fasting plasma insulin levels for the hyperglycemic and control groups at 8 weeks post-induction. Results demonstrated significant difference in blood glucose but not plasma insulin.

Figure 2

(A) Fasting blood glucose and (B) fasting plasma insulin levels for the hyperglycemic and control groups at 8 weeks post-induction. Results demonstrated significant difference in blood glucose but not plasma insulin.

Figure 3

(A) ER ROM (B) ER stiffness (C) IR ROM (D) IR stiffness for the hyperglycemic and control groups. Results demonstrated a significant decrease in ER ROM for the hyperglycemic group compared to the control group.

Figure 3

(A) ER ROM (B) ER stiffness (C) IR ROM (D) IR stiffness for the hyperglycemic and control groups. Results demonstrated a significant decrease in ER ROM for the hyperglycemic group compared to the control group.

Figure 3

(A) ER ROM (B) ER stiffness (C) IR ROM (D) IR stiffness for the hyperglycemic and control groups. Results demonstrated a significant decrease in ER ROM for the hyperglycemic group compared to the control group.

Figure 3

(A) ER ROM (B) ER stiffness (C) IR ROM (D) IR stiffness for the hyperglycemic and control groups. Results demonstrated a significant decrease in ER ROM for the hyperglycemic group compared to the control group.

Figure 4

(A) Tendon insertion site modulus (B) tendon insertion site stiffness (C) tendon insertion site cross sectional area for the hyperglycemic group and control group. Results demonstrated that there were no significant differences between the groups for any mechanical properties.

Figure 4

(A) Tendon insertion site modulus (B) tendon insertion site stiffness (C) tendon insertion site cross sectional area for the hyperglycemic group and control group. Results demonstrated that there were no significant differences between the groups for any mechanical properties.

Figure 4

(A) Tendon insertion site modulus (B) tendon insertion site stiffness (C) tendon insertion site cross sectional area for the hyperglycemic group and control group. Results demonstrated that there were no significant differences between the groups for any mechanical properties.

Figure 5

Immunohistochemistry staining density for IL1-β, AGE, & TNF-α was quantified at the insertion and midsubstance of the supraspinatus and superior capsule. A representative image for IL1-β at the supraspinatus insertion is displayed. IL1-β staining density was significantly increased (p<0.05) in the hyperglycemic group (A) compared to the control group (B).