Abstract
Rotator cuff injury (RCI) is a major musculoskeletal disorder in the adult population where inflammation and pain are major contributing factors. Coincidence of other clinical conditions like glenohumeral arthritis aggravates inflammation and delays the healing response. The mechanism and signaling factors underlying the sustenance of inflammation in the rotator cuff joint are largely unknown. The present article aims to elucidate the involvement of inflammatory molecule, TREM-1 (Triggering Receptors Expressed on Myeloid cells-1), and danger-associated molecular patterns (DAMPs), including high mobility group protein 1 (HMGB-1) and RAGE (receptor for advanced glycation end products), in the setting of RCI with respect to the severity of glenohumeral arthritis. Biceps tendons (15 specimens) from the shoulder and blood (11 samples) from patients with glenohumeral arthritis (Group-1, n = 4) and without glenohumeral arthritis (Group-2, n = 11) after RCI surgery were obtained for the study. Molecular and morphological alterations between the groups were compared using histology, immunofluorescence, RT-PCR and flow cytometry. MRI and histomorphology assessment revealed severe inflammation in Group-1 patients while in Group-2 ECM disorganization was prominent without any hallmarks of inflammation. A significant increase in TREM-1 expression in circulating neutrophils and monocytes was observed. Elevated levels of TREM-1, HMGB-1 and RAGE in Group-1 patients along with CD68+ and CD16+ cells confirmed DAMP-mediated inflammation. Expression of TREM-1 in the tendon of Group-2 patients even in the absence of immune cells presented a new population of TREM-expressing cells that were confirmed by real-time PCR analysis and immunofluorescence. Expression of HMGB-1 and RAGE in the biceps tendon from the shoulder of patients without glenohumeral arthritis implied TREM-1-mediated inflammation without involving immune cells, whereas in patients with glenohumeral arthritis, infiltration and the activation of the immune cells, primarily macrophages, release mediators to induce inflammation. This could be the reason for ECM disorganization without the classical signs of inflammation in patients without glenohumeral arthritis.
Highlights
Musculoskeletal disease is the leading cause of disability and healthcare cost in the United States [1, 2] and account for almost 20% of all healthcare visits
The purpose of this study is to investigate the role of TREM-1, High mobility group box protein 1 (HMGB-1), and RAGE in shoulder tendon tissues and systemic circulation in the setting of glenohumeral arthritis
Patients were categorized into two groups; Group-1 consists of 4 patients with severe arthritis and a rotator cuff tear and Group-2 included 11 patients with a superior labral anterior to posterior (SLAP) tear without arthritis or a full thickness rotator cuff tear
Summary
Musculoskeletal disease is the leading cause of disability and healthcare cost in the United States [1, 2] and account for almost 20% of all healthcare visits. The shoulder is the second most common site of joint pain in patients that suffer from chronic musculoskeletal disease. The most common causes of shoulder pain in the adult population are rotator cuff injuries (RCI) and glenohumeral arthritis. Inflammation associated with RCI and arthritis is a major factor in the pathogenesis of tendon function [3]. Decreasing inflammation is one of the main strategies for treating patients with rotator cuff injuries and/or arthritis. The etiological factors associated with the regulation of inflammation in RC tendon are largely unknown
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