Modeling of signaling pathways in chondrocytes based on phosphoproteomic and cytokine release data.
Objective: Chondrocyte signaling is widely identified as a key component in cartilage homeostasis. Dysregulations of the signaling processes in chondrocytes often result in degenerative diseases of the tissue. Traditionally, the literature has focused on the study of major players in chondrocyte sig...
| Publicado en: | Osteoarthritis & Cartilage Vol. 22; no. 3; pp. 509 - 519 |
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| Autores principales: | , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Elsevier B.V.
Mar2014
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=103812391&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103812391 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 10634584 NZV jtl: Osteoarthritis & Cartilage issn: 10634584 maglogo: N pubinfo: dt: Mar2014 vid: 22 iid: 3 pid: 467 pub: Elsevier B.V. place: New York, New York artinfo: ui: 103812391 NLM24457104 2012496087 10.1016/j.joca.2014.01.001 NLM24457104 103812391 ppf: 509 ppct: 10 formats: tig: atl: Modeling of signaling pathways in chondrocytes based on phosphoproteomic and cytokine release data. aug: au: Melas, I N Chairakaki, A D Chatzopoulou, E I Messinis, D E Katopodi, T Pliaka, V Samara, S Mitsos, A Dailiana, Z Kollia, P Alexopoulos, L G affil: Mechanical Engineering Department, National Technical University of Athens, Athens, Greece; Protatonce Ltd., Athens, Greece. sug: subj: Chondrocytes Cytokines Analysis Models, Biological Proteomics Human Ligands Signal Transduction ab: Objective: Chondrocyte signaling is widely identified as a key component in cartilage homeostasis. Dysregulations of the signaling processes in chondrocytes often result in degenerative diseases of the tissue. Traditionally, the literature has focused on the study of major players in chondrocyte signaling, but without considering the cross-talks between them. In this paper, we systematically interrogate the signal transduction pathways in chondrocytes, on both the phosphoproteomic and cytokine release levels.Methods: The signaling pathways downstream 78 receptors of interest are interrogated. On the phosphoproteomic level, 17 key phosphoproteins are measured upon stimulation with single treatments of 78 ligands. On the cytokine release level, 55 cytokines are measured in the supernatant upon stimulation with the same treatments. Using an Integer Linear Programming (ILP) formulation, the proteomic data is combined with a priori knowledge of proteins' connectivity to construct a mechanistic model, predictive of signal transduction in chondrocytes.Results: We were able to validate previous findings regarding major players of cartilage homeostasis and inflammation (e.g., IL1B, TNF, EGF, TGFA, INS, IGF1 and IL6). Moreover, we studied pro-inflammatory mediators (IL1B and TNF) together with pro-growth signals for investigating their role in chondrocytes hypertrophy and highlighted the role of underreported players such as Inhibin beta A (INHBA), Defensin beta 1 (DEFB1), CXCL1 and Flagellin, and uncovered the way they cross-react in the phosphoproteomic level.Conclusions: 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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