The influence of chronic IL-6 exposure, in vivo , on rat Achilles tendon extracellular matrix

Patel, Shivam; Eldon, Erica; Corbell, Kathryn; Shimkus, Kevin L.; Fluckey, James D.; Carroll, Chad C.

doi:10.1016/j.cyto.2017.04.011

Cited by 9 publications

(6 citation statements)

References 36 publications

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“…Despite differences in extraction techniques used, protein half-lives were similar in the whole tendon and the fascicular matrix, suggesting minimal effects from using different extraction techniques. Indeed, previous studies, in which the rat Achilles was acid-solubilised post deuterium labelling and FSR measured by GC-MS, reported a FSR of 0.66 % day −1 (Katsma et al, 2017) which equates to a half-life of 105 days, supporting the results we present here, in which average protein half-life in whole tendon is 131 days.…”

Section: Discussionsupporting

confidence: 91%

Heterogeneity of proteome dynamics between connective tissue phases of adult tendon

Simpson

Choi²,

Wang³

et al. 2020

Preprint

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1Maintenance of connective tissue integrity is fundamental to sustain function, requiring 2 protein turnover to repair damaged tissue. However, connective tissue proteome dynamics 3 remain largely undefined, as do differences in turnover rates of individual proteins in the 4 collagen and glycoprotein phases of connective tissue extracellular matrix (ECM). Here, we 5 investigate proteome dynamics in the collagen and glycoprotein phases of connective tissues 6 by exploiting the spatially distinct fascicular (collagen-rich) and interfascicular (glycoprotein-7 rich) ECM phases of tendon. Using isotope labelling, mass spectrometry and bioinformatics, 8 we calculate turnover rates of individual proteins within rat Achilles tendon and its ECM 9 phases. Our results demonstrate complex proteome dynamics in tendon, with ~1000-fold 10 differences in protein turnover rates, and overall faster protein turnover within the 11 glycoprotein-rich interfascicular matrix compared to the collagen-rich fascicular matrix. 12These data provide insights into the complexity of proteome dynamics in tendon, likely 13 required to maintain tissue homeostasis. 14

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Section: Discussionsupporting

confidence: 91%

Heterogeneity of proteome dynamics between connective tissue phases of adult tendon

Simpson

Choi²,

Wang³

et al. 2020

Preprint

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“…As expected, in our model, the content of IL-6 was enhanced in the presence of IL-1 β [56] and μ FAT further increased its production. This effect is possibly related to the IL-1 β -mediated induction of IL-6 in the cells contained in μ FAT [54], and even if there are little evidences of direct pathological changes mediated by IL-6 on TCs and tendon matrix production [57], this aspect should be taken into account as a possible side effect when applying cell-based regenerative medicine products. The role of IL-6 in tendon pathologies has been confirmed by several studies, and it is considered one of the evidences of inflammation involvement in tendinopathy [58].…”

Section: Discussionmentioning

confidence: 99%

Autologous Microfragmented Adipose Tissue Reduces the Catabolic and Fibrosis Response in an In Vitro Model of Tendon Cell Inflammation

Viganò

Lugano

Orfei

et al. 2019

Stem Cells International

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Background Mesenchymal stem cells (MSCs) emerged as a promising therapy for tendon pathologies. Microfragmented adipose tissue (μFAT) represents a convenient autologous product for the application of MSC-based therapies in the clinical setting. In the present study, the ability of μFAT to counteract inflammatory processes induced by IL-1β on human tendon cells (TCs) was evaluated. Methods Cell viability and proliferation were evaluated after 48 hours of transwell coculture of TCs and autologous μFAT in the presence or absence of IL-1β. Gene expression of scleraxis, collagen type I and type III, metalloproteinases-1 and -3, and cyclooxygenase-2 was evaluated by real-time RT-PCR. The content of VEGF, IL-1Ra, TNFα, and IL-6 was evaluated by ELISA. Results IL-1β-treated TCs showed augmented collagen type III, metalloproteases, and cyclooxygenase-2 expression. μFAT was able to reduce the expression of collagen type III and metalloproteases-1 in a significant manner, and at the same time, it enhanced the production of VEGF, IL-1Ra, and IL-6. Conclusions In this in vitro model of tendon cell inflammation, the paracrine action of μFAT, exerted by anti-inflammatory molecules and growth factors, was able to inhibit the expression of fibrosis and catabolic markers. Then, these results suggest that the application of μFAT may represent an effective conservative or adjuvant therapy for the treatment of tendon disorders.

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“…The role of IL-6 on differentiation of TDSCs after tendon injury in vivo remains unclear and needs to be further investigated. Katsma et al reported that chronic treatment with physiologically relevant levels of IL-6 suppresses expression of Col1a1 and LOX while also altering expression of select MMPs but does not alter Achilles tendon collagen synthesis in vivo [ 27 ]. However, as the animal model used in Katsma et al was normal rat Achilles tendon, it is still unclear how IL-6 affects TDSCs and tendon repair after tendon injury.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 Promotes Proliferation but Inhibits Tenogenic Differentiation via the Janus Kinase/Signal Transducers and Activators of Transcription 3 (JAK/STAT3) Pathway in Tendon-Derived Stem Cells

Chen

Deng

et al. 2018

Med Sci Monit

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BackgroundPrevious studies demonstrated that tendon-derived stem cells (TDSCs) were vital healing cells and that mRNA expression of anti-inflammatory cytokine IL-6 was significantly upregulated in injured tendons. The aim of the present study was to investigate the effects of IL-6 on the TDSCs in vitro.Material/MethodsTDSCs isolated from the Achilles tendons in SD rats were co-cultured with various concentrations of IL-6. Cell proliferation, cell cycle analysis, quantitative real-time PCR, western blotting analysis, and statistical analysis were used in the study.ResultsThe result showed that IL-6 strongly increased proliferation capability, and induced cell cycle activation and transition into G2/M phase from G1 phase in TDSCs. However, IL-6 treatment strongly inhibited gene expression of Scleraxis, Collagen 1, Tenomodulin, Collagen 3, Early Growth Response Protein 1, Decorin, Lumican, Biglycan and Fibromodulin in TDSCs. It also strongly inhibited protein expression of tendon cell markers like scleraxis, collagen 1, collagen 3, and tenomodulin. IL-6 treatment strongly activated the JAK/Stat3 signaling pathway in TDSCs. Furthermore, WP1066, a JAK/Stat3 signaling pathway inhibitor, abrogated the effects of IL-6 on TDSCs.ConclusionsThese findings indicated that IL-6 might exert dual effects on TDSCs in vitro: strongly enhancing their proliferation but inhibiting their tenogenic differentiation via the JAK/Stat3 pathway.

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The influence of chronic IL-6 exposure, in vivo , on rat Achilles tendon extracellular matrix

Cited by 9 publications

References 36 publications

Heterogeneity of proteome dynamics between connective tissue phases of adult tendon

Heterogeneity of proteome dynamics between connective tissue phases of adult tendon

Autologous Microfragmented Adipose Tissue Reduces the Catabolic and Fibrosis Response in an In Vitro Model of Tendon Cell Inflammation

Interleukin-6 Promotes Proliferation but Inhibits Tenogenic Differentiation via the Janus Kinase/Signal Transducers and Activators of Transcription 3 (JAK/STAT3) Pathway in Tendon-Derived Stem Cells

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