Proteomic analysis reveals rotator cuff injury caused by oxidative stress

Yuan, Tao; Qian, Hong; Yu, Xin; Meng, Jia; Lai, Chengteng; Jiang, Hui; Zhao, Jianning; Bao, Nirong

doi:10.1177/2040622320987057

Cited by 16 publications

(15 citation statements)

References 46 publications

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“…Associations between the bursa proteome and the underlying injured tendon suggested that there was cross-talk between these two tissues, although this requires further study. These findings are consistent with a study showing up-regulated markers of oxidative stress and chronic inflammation in bursa tissue from patients with rotator cuff tears compared with those with shoulder instability, indicating that the bursa proteome was dependent on the pathological state of the rotator cuff ( 29 ). The cellular makeup of healthy human bursa tissue is difficult to study because access to healthy bursa tissue samples is limited.…”

Section: Discussionsupporting

confidence: 92%

The subacromial bursa modulates tendon healing after rotator cuff injury in rats

Marshall,

Ashinsky,

Ferrer

et al. 2024

Sci. Transl. Med.

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Rotator cuff injuries result in more than 500,000 surgeries annually in the United States, many of which fail. These surgeries typically involve repair of the injured tendon and removal of the subacromial bursa, a synovial-like tissue that sits between the rotator cuff and the acromion. The subacromial bursa has been implicated in rotator cuff pathogenesis and healing. Using proteomic profiling of bursa samples from nine patients with rotator cuff injury, we show that the bursa responds to injury in the underlying tendon. In a rat model of supraspinatus tenotomy, we evaluated the bursa’s effect on the injured supraspinatus tendon, the uninjured infraspinatus tendon, and the underlying humeral head. The bursa protected the intact infraspinatus tendon adjacent to the injured supraspinatus tendon by maintaining its mechanical properties and protected the underlying humeral head by maintaining bone morphometry. The bursa promoted an inflammatory response in injured rat tendon, initiating expression of genes associated with wound healing, including Cox2 and Il6 . These results were confirmed in rat bursa organ cultures. To evaluate the potential of the bursa as a therapeutic target, polymer microspheres loaded with dexamethasone were delivered to the intact bursae of rats after tenotomy. Dexamethasone released from the bursa reduced Il1b expression in injured rat supraspinatus tendon, suggesting that the bursa could be used for drug delivery to reduce inflammation in the healing tendon. Our findings indicate that the subacromial bursa contributes to healing in underlying tissues of the shoulder joint, suggesting that its removal during rotator cuff surgery should be reconsidered.

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Section: Discussionsupporting

confidence: 92%

The subacromial bursa modulates tendon healing after rotator cuff injury in rats

Marshall,

Ashinsky,

Ferrer

et al. 2024

Sci. Transl. Med.

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“…TMAO-upregulated PLIN4 , also upregulated in brain by fasting, plays a key role in intracellular trafficking of lipids ( 97 ), lipid droplet formation, and adipocyte differentiation ( 98 ). PLIN4 was upregulated in rotator cuff injury synovium and was functionally related to oxidative stress and chronic inflammation ( 99 ). OGDHL was upregulated by a phosphorylation-dependent transcription factor CREB ( 100 ).…”

Section: Resultsmentioning

confidence: 99%

Aorta- and liver-generated TMAO enhances trained immunity for increased inflammation via ER stress/mitochondrial ROS/glycolysis pathways

Saaoud¹,

Liu²,

Xu³

et al. 2023

JCI Insight

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We determined whether gut microbiota-produced trimethylamine (TMA) is oxidized into trimethylamine N-oxide (TMAO) in non-liver tissues, whether TMAO promotes inflammation via trained immunity (TI) and made the following findings: Endoplasmic reticulum (ER) stress genes were co-upregulated with mitoCarta genes in chronic kidney diseases (CKD); TMAO upregulated 190 genes in human aortic endothelial cells (HAECs); TMAO synthesis enzyme flavin-containing monooxygenase 3 (FMO3) was expressed in human and mouse aortas,;4) TMAO trans-differentiated HAECs into innate immune cells; TMAO phosphorylated 12 kinases in cytosol via its receptor PERK and CREB, and integrated with PERK pathways; and PERK inhibitors suppressed TMAO-induced ICAM-1; TMAO upregulated 3 mitochondrial genes and downregulated inflammation inhibitor DARS2, induced mitoROS; and mitoTEMPO inhibited TMAO-induced ICAM-1; and -glucan priming followed by TMAO re-stimulation upregulated TNF- by inducing metabolic reprogramming; and glycolysis inhibitor suppressed TMAO-induced ICAM-1. Our results have provided novel insights over TMAO roles in inducing EC activation and innate immune trans-differentiation, inducing metabolic reprogramming and TI for enhanced vascular inflammation and new therapeutic targets for treating cardiovascular diseases (CVD), CKD-promoted CVD, inflammations, transplantation, aging, and cancers.

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“…Prior research has applied proteomic approach in uncovering the protein level changes along with RCT ( Sejersen et al, 2015 ; Yuan et al, 2021 ). Matrix metalloproteinases (MMPs) were found to be involved in the pathogenesis of RCT, and a remodeling of extracellular matrix (ECM) was reflected by the alteration of MMPs and collagen expression.…”

Section: Introductionmentioning

confidence: 99%

A Global Phosphorylation Atlas of Proteins Within Pathological Site of Rotator Cuff Tendinopathy

Wang

Zhang

Lin

et al. 2022

Front. Mol. Biosci.

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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.

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Proteomic analysis reveals rotator cuff injury caused by oxidative stress

Cited by 16 publications

References 46 publications

The subacromial bursa modulates tendon healing after rotator cuff injury in rats

The subacromial bursa modulates tendon healing after rotator cuff injury in rats

Aorta- and liver-generated TMAO enhances trained immunity for increased inflammation via ER stress/mitochondrial ROS/glycolysis pathways

A Global Phosphorylation Atlas of Proteins Within Pathological Site of Rotator Cuff Tendinopathy

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