title: Regulation of chondrocyte differentiation by actin-severing protein adseverin.
abstract: The importance of actin organization in controlling the chondrocyte phenotype is well established, but little is known about the cytoskeletal components regulating chondrocyte differentiation. Previously, we have observed up-regulation of an actin-binding gelsolin-like protein in hypertrophic chondrocytes. We have now identified it as adseverin (scinderin). Adseverin is drastically up-regulated during chondrocyte maturation, as shown by Northern blot analysis, in situ hybridization, and real-time RT-PCR. Its expression is positively regulated by PKC and MEK signaling as shown by inhibitory analyses. Over-expression of adseverin in non-hypertrophic chondrocytes causes rearrangement of the actin cytoskeleton, a change in cell morphology, a dramatic (3.5-fold) increase in cell volume, and up-regulation of Indian hedgehog (Ihh) and of collagen type X--all indicative of chondrocyte differentiation. These changes are mediated by ERK1/2 and p38 kinase pathways. Thus, adseverin-induced rearrangements of the actin cytoskeleton may mediate the PKC-dependent activation of p38 and Erk1/2 signaling pathways necessary for chondrocyte hypertrophy, as evidenced by changes in cell morphology, increase in cell size and expression of the chondrocyte maturation markers. These results demonstrate that interdependence of cytoskeletal organization and chondrogenic gene expression is regulated, at least in part, by actin-binding proteins such as adseverin.
authors.affiliation: Tufts University School of Medicine, Department of Anatomy and Cellular Biology, 136 Harrison Avenue Boston, MA 02111, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Nurminsky
authors.forename: Cordula
authors.initials: C
authors.lastname: Magee
authors.forename: Lidia
authors.initials: L
authors.lastname: Faverman
authors.forename: Maria
authors.initials: M
authors.lastname: Nurminskaya
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002356:Cartilage / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D048429:Cell Size; D002478:Cells, Cultured; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D024121:Collagen Type X / Q000378:metabolism; D003599:Cytoskeleton / Q000502:physiology; D018260:Gelsolin / Q000502:physiology*; D006132:Growth Plate / Q000166:cytology / Q000502:physiology; D053823:Hedgehog Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000199:Actins; D024121:Collagen Type X; D018260:Gelsolin; D053823:Hedgehog Proteins; C065395:scinderin; D011493:Protein Kinase C