Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10815473 | Cellular Signalling | 2014 | 22 Pages |
Abstract
During chondrogenesis, complex intracellular signalling pathways regulate an intricate series of events including condensation of chondroprogenitor cells and nodule formation followed by chondrogenic differentiation. Reversible phosphorylation of key target proteins is of particular importance during this process. Among protein kinases known to be involved in these pathways, protein kinase C (PKC) subtypes play pivotal roles. However, the precise function of PKC isoenzymes during chondrogenesis and in mature articular chondrocytes is still largely unclear. In this review, we provide a historical overview of how the concept of PKC-mediated chondrogenesis has evolved, starting from the first discoveries of PKC isoform expression and activity. Signalling components upstream and downstream of PKC, leading to the stimulation of chondrogenic differentiation, are also discussed. Although it is evident that we are only at the beginning to understand what roles are assigned to PKC subtypes during chondrogenesis and how they are regulated, there are many yet unexplored aspects in this area. There is evidence that calcium signalling is a central regulator in differentiating chondroprogenitors; still, clear links between intracellular calcium signalling and prototypical calcium-dependent PKC subtypes such as PKCalpha have not been established. Exploiting putative connections and shedding more light on how exactly PKC signalling pathways influence cartilage formation should open new perspectives for a better understanding of healthy as well as pathological differentiation processes of chondrocytes, and may also lead to the development of novel therapeutic approaches.
Keywords
PDBuFAKProtein kinase NFGFMSCCTGFERKPP2ANOS12-O-tetradecanoylphorbol-13-acetatePGE2PKNpKaSTIMPDDIGF-1ECMStore-operated Ca2 + entryPLCSAPKRyRCOMPPKCIP3RTGFPI-3KSOCEIHHHDCPhorbol-12-myristate-13-acetateADAMTSN-CAMIGFJnkIL-1TNFinositol-1,4,5-trisphosphate receptorEGFMMPtPACREBPhosphoprotein Phosphatase 2AADSCc-Jun N-terminal kinasecAMPPMAMAPKAdenosine TriphosphateATPCyclic adenosine monophosphateArthritisOsteoarthritisinterleukin-1transforming growth factora disintegrin and metalloproteinase with thrombospondin motifsIndian HedgehogShhdiacylglycerolDAGAdipose-derived stem cellMesenchymal stem cellendoplasmic reticulumsonic hedgehogepidermal growth factortumour necrosis factorCartilagefibroblast growth factorInsulin-like growth factorinsulin-like growth factor 1High density culturephorbol-12,13-dibutyratephospholipase CPhosphoinositol-3 kinaseExtracellular matrixmatrix metalloproteinaseBMPSignalling pathwayNitrogen monoxideneural cell adhesion moleculeProteoglycancAMP response element binding proteinCartilage oligomeric matrix proteinbone morphogenic proteinprotein kinase AProtein kinase C (PKC)Protein kinase Cmitogen-activated protein kinaseStress-activated protein kinaseProstaglandin E2ChondrocyteChondrogenesisextracellular signal-regulated kinasefocal adhesion kinaseRyanodine receptor
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Authors
Csaba Matta, Ali Mobasheri,