Targeting Inflammation in Rotator Cuff Tendon Degeneration and Repair

Abstract

Rotator cuff degeneration is a common affliction that results in pain and disability. Tendinopathy was historically classified with or without the involvement of the immune system. However, technological advancements in screening have shown that the immune system is both present and active in all forms of tendinopathy. During injury and healing, the coordinated effort of numerous immune cell populations work with the resident stromal cells to break down damaged tissues and stimulate remodeling. These cells deploy a wide array of tools, including phagocytosis, enzyme secretion, and chemotactic gradients to direct these processes. Yet, there remains a knowledge gap in our understanding of the sequence of critical events and regulatory factors that mediate this is process in injury and healing. Furthermore, current treatments do not specifically target inflammation at the molecular level. Typical regimens include non-steroidal anti-inflammatory drugs or corticosteroids; however, researchers have found irrevocable functional deficits following treatment, and have disputed their long-term efficacy. Therefore, developing therapeutics that specifically consider the nuances of the immune system are necessary to improve patient outcomes.

Depression increases the risk of rotator cuff tear and rotator cuff repair surgery: A nationwide population-based study

“…The etiology of RCT could either be extrinsic (impingement and demographic factors) or intrinsic (degeneration, hypovascularity and inflammation) [15]. Inflammation not only plays a role in the onset and development of tendon injury but also negatively impacts the repair of injured tendons [14]. Therefore, for patients with depression, the authors suggest that the intrinsic pathogenic factors, especially inflammation, might play an essential role in the development of RCT, and therefore the subsequent repair surgery.…”

“…How do depression and the associated inflammation work together in tendon injury? Depression itself might not initiate the tear of rotator cuff tendons, however inflammation could potentiate the progression of tendinopathy and tearing [14]. Furthermore, depression could amplify the painful sensation of rotator cuff disease [23,24].…”

“…Rotator cuff tear (RCT) is a common disease associated with shoulder pain and functional disability, including shoulder motion limitation and weakness [13]. The etiologies of RCT include degeneration, sports injury and trauma [14]. Some risk factors of RCT, including aging, obesity and diabetes mellitus (DM) are known to increase circulating inflammatory factors [15, 16].…”

Effects of EDC-PEI heparinization on allogeneic vascular antigens and inflammation levels via a rat abdominal aorta transplantation model

“…In the early stage of inflammatory response, inflammatory cells and inflammatory factors can stimulate the mobilization and homing of endothelial progenitor cells, which is conducive to damage repair ( 18 ). However, the long-term inflammatory stimuli and high-level inflammatory factors can reduce the number of endothelial progenitor cells in circulation, accelerate the apoptosis of endothelial progenitor cells, and inhibit the adhesion and proliferation of endothelial progenitor cells, thus harming the damage repair and leading to the occurrence and development of vascular injury after transplantation ( 19 – 21 ). In this study, the aorta was thickened, the lumen was narrow, and a large number of inflammatory cells were accumulated in the middle membrane in the control group.…”

Polymorphisms and alterations in gene expression associated with rotator cuff tear and healing following surgical repair: a systematic review

“…74,84 Studies that selected controls based on a known diagnosis of impingement syndrome, adhesive capsulitis, or other inflammatory shoulder diseases were excluded as these conditions have been associated with RCTs, which can confound results. 1,26,31,41 Studies were included irrespective of the cause or known duration of RCTs, as many tears have a subacute-onchronic or chronic-on-subacute pattern, making such a classification unreliable. 81 No restraints were implemented for subject age or RCT type or size.…”