Logo Abstract Information

Presenting Author(s) Nancy Schwartz
Abstract Title Altered Gene Expression in Aggrecan-deficient Growth Plate.
Full author List Nancy B. Schwartz and Miriam Domowicz
Text of abstract Heritable disorders causing deficiency of the connective tissue macromolecule aggrecan, in both chick and mouse, produce abnormal phenotypes including fetal dwarfism and premature death, demonstrating the essential involvement of aggrecan in development.  Although failure of bone growth is a prominent feature of these phenotypes, the role of aggrecan in growth plate development has not been defined.  In the aggrecan-deficient nanomelic (nm) chick mutant, the normal cytoarchitecture of the growth plate, proliferative capacity and degree of cell death, are all markedly altered.  The expression patterns of chondrocytic markers and signaling molecules considered essential for chondrogenesis and endochondral bone development was investigated by in situ hybridization in the nm cartilage. In the wild type (wt) chick femur growth plate there is clear distinction of the areas expressing indian hedgehog (Ihh), collagen X and osteopontin, characteristic of pre-hypertrophic, hypertrophic and late hypertrophic chondrocytes, respectively; while in the nm mutant these markers are all expressed in the same area.  The absence of aggrecan is also accompanied by discordant gene expression of BMP6, PTHrP (parathyroid hormone-related peptide receptor) and SOX9, all proposed to be involved in regulating growth plate maturation.    In contrast, other structural molecules, e.g. collagen type IX, collagen type II or tenascin and the marker of osteoblasts, osteocalcin, had comparable patterns of expression in the wt and nm growth plate. Analysis at early stages of limb development (E7-E8) indicates that an acceleration of differentiation to hyperthrophic chondrocytes, initiated by deregulation of the expression of Ihh, underline the phenotypic differences observed in the nm mutant. Taken together these observations indicate that aggrecan is a key component in regulating the transition to chondrocyte hypertrophy.
Which session is your work most relevant to: Tissue differentiation