Tenocyte activation and regulation of complement factors in response to in vitro cell injury

Girke, Georg; Kohl, Benjamin; Busch, Catharina; John, Thilo; Godkin, Owen; Ertel, Wolfgang; Schulze‐Tanzil, Gundula

doi:10.1016/j.molimm.2014.03.008

Cited by 13 publications

(10 citation statements)

References 29 publications

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“…Based on our observations using a previously explored in vitro injury model we propose that acute injury induces CCL2 mediated monocyte recruitment 44 . Here, soluble factors or biologically active ECM fragments induce subsequent release of S100A8 and S100A9 from monocytes that will, in turn, bind receptors on the tenocyte surface and stimulate release of further inflammatory factors (Fig.…”

Section: Discussionmentioning

confidence: 77%

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S100A8 & S100A9: Alarmin mediated inflammation in tendinopathy

Crowe

McLean

Kitson

et al. 2019

Sci Rep

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Alarmins S100A8 and S100A9 are endogenous molecules released in response to environmental triggers and cellular damage. They are constitutively expressed in immune cells such as monocytes and neutrophils and their expression is upregulated under inflammatory conditions. The molecular mechanisms that regulate inflammatory pathways in tendinopathy are largely unknown therefore identifying early immune effectors is essential to understanding the pathology. Based on our previous investigations highlighting tendinopathy as an alarmin mediated pathology we sought evidence of S100A8 & A9 expression in a human model of tendinopathy and thereafter, to explore mechanisms whereby S100 proteins may regulate release of inflammatory mediators and matrix synthesis in human tenocytes. Immunohistochemistry and quantitative RT-PCR showed S100A8 & A9 expression was significantly upregulated in tendinopathic tissue compared with control. Furthermore, treating primary human tenocytes with exogenous S100A8 & A9 significantly increased protein release of IL-6, IL-8, CCL2, CCL20 and CXCL10; however, no alterations in genes associated with matrix remodelling were observed at a transcript level. We propose S100A8 & A9 participate in early pathology by modulating the stromal microenvironment and influencing the inflammatory profile observed in tendinopathy. S100A8 and S100A9 may participate in a positive feedback mechanism involving enhanced leukocyte recruitment and release of pro-inflammatory cytokines from tenocytes that perpetuates the inflammatory response within the tendon in the early stages of disease.

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Section: Discussionmentioning

confidence: 77%

“…Normal tenocytes were seeded at 5 × 10 4 /ml in 12 well culture plates and scratched 4 times across the diameter of the plate with a sterile pipette tip. Injured cells were incubated for 24 hours before harvesting of supernatants 44,51 .…”

Section: Methodsmentioning

confidence: 99%

S100A8 & S100A9: Alarmin mediated inflammation in tendinopathy

Crowe

McLean

Kitson

et al. 2019

Sci Rep

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“…In recent years, the involvement of complement activation has been strongly implicated in OA and synovitis [8,9,22,129]. Complement could also contribute to tendon degeneration since complement regulatory components are expressed in tenocytes, and the complement split fragment C3a elicited a catabolic response in tenocytes as shown by in vitro studies [130,131]. IL-6, which is present under OA condition but also the complement split fragment anaphylatoxin C3a, which is released during activation of the complement cascade, impaired the gene expression of cytoprotective complement regulatory proteins (CRP) in tenocytes.…”

Section: Candidate Signaling Pathways Involved In Ligament Degenermentioning

confidence: 99%

Intraarticular Ligament Degeneration Is Interrelated with Cartilage and Bone Destruction in Osteoarthritis

Schulze‐Tanzil

2019

Cells

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Osteoarthritis (OA) induces inflammation and degeneration of all joint components including cartilage, joint capsule, bone and bone marrow, and ligaments. Particularly intraarticular ligaments, which connect the articulating bones such as the anterior cruciate ligament (ACL) and meniscotibial ligaments, fixing the fibrocartilaginous menisci to the tibial bone, are prone to the inflamed joint milieu in OA. However, the pathogenesis of ligament degeneration on the cellular level, most likely triggered by OA associated inflammation, remains poorly understood. Hence, this review sheds light into the intimate interrelation between ligament degeneration, synovitis, joint cartilage degradation, and dysbalanced subchondral bone remodeling. Various features of ligament degeneration accompanying joint cartilage degradation have been reported including chondroid metaplasia, cyst formation, heterotopic ossification, and mucoid and fatty degenerations. The entheses of ligaments, fixing ligaments to the subchondral bone, possibly influence the localization of subchondral bone lesions. The transforming growth factor (TGF)β/bone morphogenetic (BMP) pathway could present a link between degeneration of the osteochondral unit and ligaments with misrouted stem cell differentiation as one likely reason for ligament degeneration, but less studied pathways such as complement activation could also contribute to inflammation. Facilitation of OA progression by changed biomechanics of degenerated ligaments should be addressed in more detail in the future.

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“…80 Ligaments and tendons express complement factors. 81,82 The complement split fragment C3a, which is produced during the early phase of inflammation, induces gene expression of the anaphylatoxin receptors, C3aR and C5aR, as well as expression of the pro-inflammatory cytokines TNF-α and IL-1β. Furthermore, it impairs the gene expression of the cytoprotective CRPs, CD46 and CD55, in human tenocytes in vitro.…”

Section: Sources For Complement In the Jointmentioning

confidence: 99%

Osteoarthritis and the Complement Cascade

Silawal

Triebel

Bertsch

et al. 2018

Clin Med�Insights�Arthritis�Musculoskelet Disord

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Accumulating evidence demonstrates that complement activation is involved in the pathogenesis of osteoarthritis (OA). However, the intimate complement regulation and cross talk with other signaling pathways in joint-associated tissues remain incompletely understood. Recent insights are summarized and discussed here, to put together a more comprehensive picture of complement involvement in OA pathogenesis. Complement is regulated by several catabolic and inflammatory mediators playing a key role in OA. It seems to be involved in many processes observed during OA development and progression, such as extracellular cartilage matrix (ECM) degradation, chondrocyte and synoviocyte inflammatory responses, cell lysis, synovitis, disbalanced bone remodeling, osteophyte formation, and stem cell recruitment, as well as cartilage angiogenesis. In reverse, complement can be activated by various ECM components and their cleavage products, which are released during OA-associated cartilage degradation. There are, however, some other cartilage ECM components that can inhibit complement, underlining the diverse effects of ECM on the complement activation. It is hypothesized that complement might also be directly activated by mechanical stress, thereby contributing to OA. The question arises whether keeping the complement activation in balance could represent a future therapeutic strategy in OA treatment and in the prevention of its progression.

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Tenocyte activation and regulation of complement factors in response to in vitro cell injury

Cited by 13 publications

References 29 publications

S100A8 & S100A9: Alarmin mediated inflammation in tendinopathy

S100A8 & S100A9: Alarmin mediated inflammation in tendinopathy

Intraarticular Ligament Degeneration Is Interrelated with Cartilage and Bone Destruction in Osteoarthritis

Osteoarthritis and the Complement Cascade

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