Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS

Final Activity Report Summary - FISHBONEP (Role of Parathyroid Hormone related Protein (PTHrP) in endochondral bone development: Application as a possible marker for skeletal anomalies in fish)

The following is a brief summary of the completed studies on the role of osteonectin in endochondral bone development. Osteonectin is a matricellular glycoprotein expressed in many differentiated cells which is critical for organ development and cell processes such as cell turnover, remodelling and tissue repair. Osteonectin, well conserved in evolution, is a major non-collagenous constituent of vertebrate bones. Growing bodies of evidences indicate that ostonectin could play a role in cell differentiation, particularly in chondrocytes. However, a precise role for osteonectin and its regulation in chondrogenesis is known.

We therefore used a morpholino-based knockdown approach to investigate the functions of osteonectin. During zebrafish embryo development, osteonectin was expressed in the notochord, floor plate, esclerotome, otic vesicle, eye and epidermal fin folds. However, its expression was tightly regulated in cartilage structures. The morphant embryos showed reductions in Meckel's cartilage, small kinked ceratohyals and shorter pectoral fins. In morpholino-injected animals the expression of col2a1 was strongly decreased but did not influence sox9 expression. Moreover, we found that osteonectin expression was down-regulated in sox9 mutant embryos.
% In addition, knockdown of osteonectin led to defective semicircular channels without affecting the otoliths. As a consequence, the morphant larvae failed to balance. These phenotypes were osteonectin-specific because osteonectin messenger Ribonucleic acid (mRNA) lacking morpholino recognising site rescued morphant phenotypes.

Thus, this study provided the first characterisation of the involvement of osteonectin in chondrocyte differentiation, showed that osteonectin acted downstream of sox9 in a cascade of genes' regulation and indicated that osteonectin was a possible modulator of chondrogenesis.

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