Modeling of signaling pathways in chondrocytes based on phosphoproteomic and cytokine release data

Melas, Ioannis N.; Chairakaki, Aikaterini D.; Chatzopoulou, Elli; Messinis, Dimitris E; Katopodi, Theoni; Pliaka, Vaia; Samara, S.; Mitsos, Alexander; Dailiana, Zoe; Κollia, Panagoula; Alexopoulos, Leonidas G.

doi:10.1016/j.joca.2014.01.001

Cited by 34 publications

(34 citation statements)

References 39 publications

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“…One of the previous studies suggests that both these proteins directly affect the chondrocyte metabolism during chondrogenesis and osteogenesis which might be involved in bone modelling. Inhibin beta A function as progrowth signalling molecule in chondrocytes hypertrophy [62]. Inhibin and activins are involved in different pathophysiological conditions.…”

Section: Growth Factors In Chondrocyte Development Cartilage Mainmentioning

confidence: 99%

Applications of Chondrocyte-Based Cartilage Engineering: An Overview

Phull

Abbas

et al. 2016

BioMed Research International

111

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Chondrocytes are the exclusive cells residing in cartilage and maintain the functionality of cartilage tissue. Series of biocomponents such as different growth factors, cytokines, and transcriptional factors regulate the mesenchymal stem cells (MSCs) differentiation to chondrocytes. The number of chondrocytes and dedifferentiation are the key limitations in subsequent clinical application of the chondrocytes. Different culture methods are being developed to overcome such issues. Using tissue engineering and cell based approaches, chondrocytes offer prominent therapeutic option specifically in orthopedics for cartilage repair and to treat ailments such as tracheal defects, facial reconstruction, and urinary incontinence. Matrix-assisted autologous chondrocyte transplantation/implantation is an improved version of traditional autologous chondrocyte transplantation (ACT) method. An increasing number of studies show the clinical significance of this technique for the chondral lesions treatment. Literature survey was carried out to address clinical and functional findings by using various ACT procedures. The current study was conducted to study the pharmacological significance and biomedical application of chondrocytes. Furthermore, it is inferred from the present study that long term follow-up studies are required to evaluate the potential of these methods and specific positive outcomes.

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Section: Growth Factors In Chondrocyte Development Cartilage Mainmentioning

confidence: 99%

Applications of Chondrocyte-Based Cartilage Engineering: An Overview

Phull

Abbas

et al. 2016

BioMed Research International

111

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“…Thus, these studies also provided compelling evidence that the pro- and anti-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-4, IL-6, IL-15, IL-10, IL-13, IL-15, IL-17, IL-18, IL-21, as well as chemokines, such as monocyte chemotactic protein-1 (MCP-1), fractalkine and IL-8, transcription factors, such as NF-κB and NFAT1, members of the bone morphogenetic protein family including the BMP, WNT, GREM1, FRZB and DKK1 genes, growth factors, such as transforming growth factor-β, vascular endothelial growth factor, and epidermal growth factor [20, 21], leukemia inhibitory factor [22, 23], hormonally-stimulated pain pathways, and OA susceptibility genes, such as GDF5 , all appear to be vital components germane to the OA process [24–38]. Thus, it is likely that further understanding of how a balance between the pro-inflammatory and anti-inflammatory cytokine repertoire is maintained will not only reveal the complexity inherent in regulating the destruction of synovial joints in OA, but will also be instructive for designing interventional strategies that would have been completely ignored 20 or more years ago.…”

Section: Introductionmentioning

confidence: 99%

Biologic basis of osteoarthritis

Malemud

2015

Current Opinion in Rheumatology

145

113

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Purpose of Review Evidence accumulated since 2010 indicates that human osteoarthritis should now be reclassified as a systemic musculoskeletal disease rather than a focal disorder of synovial joints. Recent Findings Inflammation was seen as the key component promoting synovitis as well as progression of cartilage and bone destruction in osteoarthritis. Thus, metabolic-triggered inflammation involving cytokines, adipokines, abnormal metabolites, acute phase reactants and even complement, all appear to play major roles in OA pathophysiology. Immune-mediated inflammation involving T- and B-cells as well as macrophages is now considered a common finding in OA synovial tissue. Many experimental and clinical analyses showed that the pro-inflammatory cytokines which stimulate matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motif gene transcription in normal and OA human chondrocyte cultures are also present at significantly elevated levels in the synovial fluid of OA patients compared to non-arthritic synovial fluids. Summary Human osteoarthritis is a systemic musculoskeletal disorder involving activation of innate and adaptive immune systems accompanied by inflammation exemplified by the elevated production of pro-inflammatory cytokines which play a significant role in the progression of the disease. The future of novel therapies for osteoarthritis should consider developing drug development strategies designed to inhibit pro-inflammatory cytokine-induced signal transduction. These strategies have been successful in the development of drugs for the treatment of rheumatoid arthritis.

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“…Melas et al (26) found that cultured chondrocytes may release up to 55 cytokines and other active agents either spontaneously or after stimulation by various ligands and list of growth factors produced by chondrocyte may still not be complete. Thus, in view of the powerful influence exerted by CIF both on the synovial membrane (14) and CLFs as evident in this work, further studies on its composition are needed, particularly that improved CIF like-cocktail could find application in treatment of various joint or tendon ailments.…”

Section: Discussionmentioning

confidence: 99%

Influence of cartilage interstitial fluid on gene expression in cruciate ligament fibroblasts

et al. 2017

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Abstract. Loading of articular cartilage during motion squeezes the fluid from the cartilage, termed cartilage interstitial fluid (CIF), which was found to influence gene expression in synovial membrane cells. After crucial ligaments damage, these cells are exposed to synovial fluid containing factors released from articular cartilage; the aim of the present study was to establish the influence of CIF and factors present in CIF (CIF-like cocktails) on crucial ligament fibroblasts. CIF was squeezed from articular-epiphyseal cartilage complexes of newborn rats. Fibroblasts were obtained from crucial ligaments of adult rat knee joints. Cells were cultured in control medium, CIF and CIF-like cocktails, and the expression of selected genes was evaluated using quantitative PCR. CIF stimulated the expression of HAS1, HAS2, aggrecan, lubricin, MMP3, TIMP3 and TGFβ1. Expression of collagen type I, versican, MMP2, TIMP2, TNF and IL1β was inhibited. The CIF-like cocktail stimulated HAS1, HAS2, collagen type I, versican, aggrecan, lubricin, TIMP1, TGFβ1, IL1β, IL6 and inhibited of MMP3 and TNF expression. Both agents exerted similar effects on the expression of HAS2, aggrecan, lubricin, TGFβ1 and TNF. CIF contains inhibitory and stimulatory factors affecting gene expression in crucial ligament fibroblasts and some of them were not included in the CIF-like cocktail. Due to the powerful influence of CIF on crucial ligament fibroblasts and the synovial membrane, further studies on its composition are needed. An improved CIF like-cocktail could be applied in the treatment of various joint or tendon ailments.

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Modeling of signaling pathways in chondrocytes based on phosphoproteomic and cytokine release data

Abstract: The analysis presented herein, leveraged high throughput proteomic data via an ILP formulation to gain new insight into chondrocytes signaling and the pathophysiology of degenerative diseases in articular cartilage.

Cited by 34 publications

References 39 publications

Applications of Chondrocyte-Based Cartilage Engineering: An Overview

Applications of Chondrocyte-Based Cartilage Engineering: An Overview

Biologic basis of osteoarthritis

Influence of cartilage interstitial fluid on gene expression in cruciate ligament fibroblasts

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