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.