![]() ECM proteins directly and indirectly modulate signal transduction pathways triggered by growth and differentiation factors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist.Ĭells differentiate in response to environmental signals from their neighbors and also from extracellular matrix (ECM) effectors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This research was supported in part by National Institutes of Health (NIH) grants GM066882 (KBM) and RC4-AR060546 (MBG and KBM) the CARISBO Foundation of Bologna, Italy (EO, SP and Andrea Facchini) FIRB-MIUR of Italy grant RBAP10KCNS (Andrea Facchini, FF, DP, Annalisa Facchini and RMB) Fondi cinque per mille (Ministero della Salute, Italy) (Andrea Faccchini, DP and RMB) POS-FESR 2007–2013, Emilia Romagna Region (EO) and also in part by an Arthritis Foundation postdoctoral fellowship (MO) and an Osteoarthritis Research Society International scholarship (EO). Received: MaAccepted: JPublished: September 2, 2013Ĭopyright: © 2013 Olivotto et al. PLoS ONE 8(9):Įditor: Florence Ruggiero, UMR CNRS 5242 - ENS de Lyon- Université Lyon 1, France (2013) IKKα/CHUK Regulates Extracellular Matrix Remodeling Independent of Its Kinase Activity to Facilitate Articular Chondrocyte Differentiation. ![]() Importantly, the differentiation of IKKα-deficient chondrocytes was rescued by a kinase-dead IKKα protein mutant.Ĭitation: Olivotto E, Otero M, Astolfi A, Platano D, Facchini A, Pagani S, et al. ![]() IKKα deficiency suppressed chondrocyte differentiation, as shown by the quantitative inhibition of.Alizarin red staining and the reduced expression of multiple chondrocyte differentiation effectors, including Runx2, Col10a1 and Vegfa. MMP-13 and total collagenase activities were significantly reduced, while TIMP-3 (tissue inhibitor of metalloproteinase-3) protein levels were enhanced in IKKα-deficient chondrocytes. ECM integrity, as assessed by type II collagen (COL2) deposition and the lack of MMP-dependent COL2 degradation products, was enhanced by IKKα ablation in mice. MMP-10 was identified as a major target of IKKα in chondrocytes by mRNA profiling, quantitative RT-PCR analysis, immunohistochemistry and immunoblotting. IKKα expression was ablated in primary human osteoarthritic (OA) chondrocytes and in immature murine articular chondrocytes (iMACs) derived from IKKα f/f:CreERT2 mice by retroviral-mediated stable shRNA transduction and Cre recombinase-dependent Lox P site recombination, respectively.
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