The inflammatory response of the supraspinatus muscle in rotator cuff tear conditions

Frich, Lars Henrik; Rosa-Fernandes, Lívia; Hejbøl, Eva Kildall; Nielsen, Pernille Vinther; Jørgensen, Puk Hvirgel; Stensballe, Allan; Lambertsen, Kate Lykke

doi:10.1016/j.jse.2020.08.028

Cited by 28 publications

(16 citation statements)

References 51 publications

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“…The role of the macrophage is an area of emerging interest in tendinopathy and tendon healing [ 24 , 25 ]. Indeed, inflammation appears to be driven by a high number of infiltrating macrophages at the inflamed tendon site [ 24 ]. Furthermore, diseased tendons from patients with tendinopathy show an abundance of CD14 + and CD68 + activated cells [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

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Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes

et al. 2021

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Sustained oxidative stress and inflammation have been reported as the major factors responsible for the failure of tendon healing during rotator cuff tears (RCTs) and rotator cuff disease (RCD). Although, their therapeutic management remains still challenging. Carbonic anhydrases (CAs) are involved in many pathological conditions, and the overexpression of both CA9 and 12 in inflamed joints has been recently reported. Consequently, a selective CA9/12 inhibition could be a feasible strategy for improving tendon recovery after injury. In addition, since carbon monoxide (CO) has been proven to have an important role in modulating inflammation, CO releasing molecules (CORMs) can be also potentially suitable compounds. The present study aims at evaluating five newly synthesized dual-mode acting CA inhibitors (CAIs)-CORMs compounds, belonging to two chemical scaffolds, on tendon-derived human primary cells under H2O2 stimulation in comparison with Meloxicam. Our results show that compounds 2 and 7 are the most promising of the series in counteracting oxidative stress-induced cytotoxicity and display a better profile in terms of enhanced viability, decreased LDH release, and augmented tenocyte proliferation compared to Meloxicam. Moreover, compound 7, as a potent superoxide scavenger, exerts its action inhibiting NF-ĸB translocation and downregulating iNOS, whereas compound 2 is more effective in increasing collagen I deposition. Taken together, our data highlight a potential role of CA in RCTs and RCD and the prospective effectiveness of compounds acting as CAI-CORM during inflammation.

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Section: Resultsmentioning

confidence: 99%

Section: Establishment Of the Inflammatory Cell Model And Preliminary Investigationsmentioning

confidence: 99%

Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes

et al. 2021

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“…In this light, the role of the macrophage is an area of emerging interest in tendinopathies and in general in the healing of tendons. In fact, inflammation appears to be driven by a high number of infiltrating macrophages at the inflamed tendon site [ 47 ]. Furthermore, damaged tendons from patients with tendinopathy show an abundance of CD14 + and CD68 + activated macrophages [ 48 ].…”

Section: Resultsmentioning

confidence: 99%

A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes

et al. 2021

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Carbon monoxide (CO) can prevent cell and tissue damage by restoring redox homeostasis and counteracting inflammation. CO-releasing molecules (CORMs) can release a controlled amount of CO to cells and are emerging as a safer therapeutic alternative to delivery of CO in vivo. Sustained oxidative stress and inflammation can cause chronic pain and disability in tendon-related diseases, whose therapeutic management is still a challenge. In this light, we developed three small subsets of 1,5-diarylpyrrole and pyrazole dicobalt(0)hexacarbonyl (DCH)-CORMs to assess their potential use in musculoskeletal diseases. A myoglobin-based spectrophotometric assay showed that these CORMs act as slow and efficient CO-releasers. Five selected compounds were then tested on human primary-derived tenocytes before and after hydrogen peroxide stimulation to assess their efficacy in restoring cell redox homeostasis and counteracting inflammation in terms of PGE2 secretion. The obtained results showed an improvement in tendon homeostasis and a cytoprotective effect, reflecting their activity as CO-releasers, and a reduction of PGE2 secretion. As these compounds contain structural fragments of COX-2 selective inhibitors, we hypothesized that such a composite mechanism of action results from the combination of CO-release and COX-2 inhibition and that these compounds might have a potential role as dual-acting therapeutic agents in tendon-derived diseases.

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“…Similarly, interleukin 1 beta has been tied to catabolic effects on tendons and increases COMP production 68 . Proteomic profiling demonstrated that migrating macrophages heavily influence the outcome in the initial degeneration stages 69 .…”

Section: Discussion Of Literaturementioning

confidence: 99%

Tendon and multiomics: advantages, advances, and opportunities

Sarmiento

Little

2021

npj Regen Med

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Tendons heal by fibrosis, which hinders function and increases re-injury risk. Yet the biology that leads to degeneration and regeneration of tendons is not completely understood. Improved understanding of the metabolic nuances that cause diverse outcomes in tendinopathies is required to solve these problems. ‘Omics methods are increasingly used to characterize phenotypes in tissues. Multiomics integrates ‘omic datasets to identify coherent relationships and provide insight into differences in molecular and metabolic pathways between anatomic locations, and disease stages. This work reviews the current literature pertaining to multiomics in tendon and the potential of these platforms to improve tendon regeneration. We assessed the literature and identified areas where ‘omics platforms contribute to the field: (1) Tendon biology where their hierarchical complexity and demographic factors are studied. (2) Tendon degeneration and healing, where comparisons across tendon pathologies are analyzed. (3) The in vitro engineered tendon phenotype, where we compare the engineered phenotype to relevant native tissues. (4) Finally, we review regenerative and therapeutic approaches. We identified gaps in current knowledge and opportunities for future study: (1) The need to increase the diversity of human subjects and cell sources. (2) Opportunities to improve understanding of tendon heterogeneity. (3) The need to use these improvements to inform new engineered and regenerative therapeutic approaches. (4) The need to increase understanding of the development of tendon pathology. Together, the expanding use of various ‘omics platforms and data analysis resulting from these platforms could substantially contribute to major advances in the tendon tissue engineering and regenerative medicine field.

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The inflammatory response of the supraspinatus muscle in rotator cuff tear conditions

Cited by 28 publications

References 51 publications

Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes

Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes

A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes

Tendon and multiomics: advantages, advances, and opportunities

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