Research Article: Genome-Wide Analyses of Gene Expression during Mouse Endochondral Ossification

Date Published: January 13, 2010

Publisher: Public Library of Science

Author(s): Claudine G. James, Lee-Anne Stanton, Hanga Agoston, Veronica Ulici, T. Michael Underhill, Frank Beier, Mauricio Rojas.

Abstract: Endochondral ossification is a complex process involving a series of events that are initiated by the establishment of a chondrogenic template and culminate in its replacement through the coordinated activity of osteoblasts, osteoclasts and endothelial cells. Comprehensive analyses of in vivo gene expression profiles during these processes are essential to obtain a complete understanding of the regulatory mechanisms involved.

Partial Text: Endochondral ossification (EO) is the process through which the axial and appendicular skeletal elements form via a transient cartilaginous intermediate [1], [2]. The development of temporary cartilage involves the differentiation of mesenchymal precursor cells along the chondrogenic lineage. The different stages of this developmental program occur in a well-defined region, known as the growth plate [3]. In the growth plate, chondrocytes progress through each step of their life cycle in a spatial pattern where cell morphology correlates with the temporal progression of chondrocyte maturation. The region nearest to the end of the bone is the outermost growth plate zone or resting zone. Chondrocytes in this zone appear small and rounded and likely provide the cellular pool for both future articular chondrocytes and chondrocytes undergoing the subsequent stages of growth plate differentiation. The proliferative zone of the growth plate lies adjacent to the resting zone and is populated with actively dividing chondrocytes arranged in characteristic columns of disc-shaped cells. Upon completion of the proliferative period, chondrocytes mature to hypertrophic chondrocytes, which, as their name suggests, are enlarged cells that constitute the hypertrophic zone. When chondrocytes terminally differentiate, they undergo apoptosis, leaving behind a calcified extracellular matrix (ECM) that is remodeled and degraded by invading blood vessels, osteoprogenitor cells and bone-resorbing cells. This coordinated developmental process of chondrocyte proliferation and differentiation is ultimately responsible for longitudinal bone growth and the final length of mature bone.



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