Abstract
Rotator cuff tendinopathy (RCT) is the most common cause of shoulder pain, therefore posing an important clinical problem. Understanding the mechanism and biochemical changes of RCT would be of crucial importance and pave the path to targeting novel and effective therapeutic strategies in translational perspectives and clinical practices. Phosphorylation, as one of the most important and well-studied post-translational modifications, is tightly associated with protein activity and protein functional regulation. Here in this study, we generated a global protein phosphorylation atlas within the pathological site of human RCT patients. By using Tandem Mass Tag (TMT) labeling combined with mass spectrometry, an average of 7,741 phosphorylation sites (p-sites) and 3,026 proteins were identified. Compared with their normal counterparts, 1,668 p-sites in 706 proteins were identified as upregulated, while 73 p-sites in 57 proteins were downregulated. GO enrichment analyses have shown that majority of proteins with upregulated p-sites functioned in neutrophil-mediated immunity whereas downregulated p-sites are mainly involved in muscle development. Furthermore, pathway analysis identified NF-κB–related TNF signaling pathway and protein kinase C alpha type (PKCα)–related Wnt signaling pathway were associated with RCT pathology. At last, a weighted kinase-site phosphorylation network was built to identify potentially core kinase, from which serine/threonine-protein kinase 39 (STLK3) and mammalian STE20-like protein kinase 1 (MST1) were proposed to be positively correlated with the activation of Wnt pathway.
Highlights
Tendinopathy is a term used to describe a complex multi-faceted pathology of the tendon characterized by pain, decline in function, and reduced exercise tolerance
Diagnosis of Rotator cuff tendinopathy (RCT) was based on the existing guideline, which takes into account the symptom, physical examination, and MRI reports
Protein phosphorylation is of great importance for the coordination of cellular and organic functions including the regulation of metabolism, proliferation, apoptosis, subcellular trafficking, inflammation, and other important physiological processes
Summary
Tendinopathy is a term used to describe a complex multi-faceted pathology of the tendon characterized by pain, decline in function, and reduced exercise tolerance. Patients with rotator cuff tendinopathy (RCT) comprise a sizeable portion of this subpopulation, and RCT is the most common cause of shoulder pain. Rotator cuff disorders are a significant source of morbidity among manual laborers and those whose work involves a great deal of repetitive motion. According to the existing guideline, orthopedic surgical referral is obtained if nonoperative therapy fails to provide relief within 6–9 months or a diagnosis of rotator cuff tear is made. A good prognosis still could barely be guaranteed, not to say that patients have to bear sustainable pain and a significant loss of shoulder range of motion. Understanding the mechanism and biochemical changes of RCT so as to provide more therapeutic options for this condition is of crucial importance
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