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During appendicular skeletal development, the bi-potential cartilage anlagen gives rise to transient cartilage, which is eventually replaced by bone, and to articular cartilage that caps the ends of individual skeletal elements. While the molecular mechanism that regulates transient cartilage differentiation is relatively well understood, the mechanism of articular cartilage differentiation has only begun to be unraveled. Furthermore, the molecules that coordinate the articular and transient cartilage differentiation processes are poorly understood. Here, we have characterized in chick the regulatory roles of two transcription factors, NFIA and GATA3, in articular cartilage differentiation, maintenance and the coordinated differentiation of articular and transient cartilage. Both NFIA and GATA3 block hypertrophic differentiation. Our results suggest that NFIA is not sufficient but necessary for articular cartilage differentiation. Ectopic activation of GATA3promotes articular cartilage differentiation, where as inhibition of GATA3 activity promotes transient cartilage differentiation at the expense of articular cartilage. We propose a novel transcriptional circuitry involved in embryonic articular cartilage differentiation, maintenance and its crosstalk with the transient cartilage differentiation program. [ABSTRACT FROM AUTHOR]

During appendicular skeletal development, the bi-potential cartilage anlagen gives rise to transient cartilage, which is eventually replaced by bone, and articular cartilage which caps the ends of individual skeletal elements. While the molecular mechanism that regulates transient cartilage differentiation is relatively better understood, the mechanism of articular cartilage differentiation has only begun to be unraveled. Further, the molecules that coordinate articular and transient cartilage differentiation processes are very poorly understood. Here, we have characterized the regulatory roles of two transcription factors, NFIA and GATA3 in articular cartilage differentiation, maintenance and the coordinated differentiation of articular and transient cartilage. Both NFIA and GATA3 block hypertrophic differentiation. Our results suggest that NFIA is not sufficient but necessary for articular cartilage differentiation. On the other hand, while ectopic activation of GATA3 promotes articular cartilage differentiation, inhibition of GATA3 activity promotes transient cartilage differentiation at the expense of articular cartilage. Finally, we propose a novel transcriptional circuitry involved in embryonic articular cartilage differentiation, maintenance and its crosstalk with transient cartilage differentiation program. [ABSTRACT FROM AUTHOR]

Articular cartilage present at the ends of appendicular skeletal elements provides friction-less movement to the synovial joints and any damage to this tissue can lead to a degenerative disease of joint called osteoarthritis. During past two decades although many genes e.g.,Gdf5, Wnt9a , Noggin etc. have been identified and characterized in joint development, still a comprehensive understanding of molecular network(s) operational in articular cartilage morphogenesis is far from being drawn. Here we report identification of 36 genes (19 from literature survey and 17 from microarray analysis) that are expressed in developing chicken phalangeal joints in a spatiotemporally dynamic manner. For both these set of genes across the time window investigated we observed three kinds of expression patterns: early, late and constant. The early expressed genes are invariably expressed in a domain broader than the interzone while the late expressed genes are expressed in restricted spatial domains. The comprehensive expression analysis presented in this report provides a candidate list of molecular players involved in articular cartilage differentiation and/or maintenance. [ABSTRACT FROM AUTHOR]

The articular cartilage, which lines the joints of the limb skeleton, is distinct from the adjoining transient cartilage, and yet, it differentiates as a unique population within a contiguous cartilage element. Current literature suggests that articular cartilage and transient cartilage originate from different cell populations. Using a combination of lineage tracing and pulse-chase of actively proliferating chondrocytes, we here demonstrate that, similar to transient cartilage, embryonic articular cartilage cells also originate from the proliferating chondrocytes situated near the distal ends of skeletal anlagen. We show that nascent cartilage cells are capable of differentiating as articular or transient cartilage, depending on exposure to Wnt or BMP signaling, respectively. The spatial organization of the articular cartilage results from a band of Nogexpressing cells, which insulates these proliferating chondrocytes from BMP signaling and allows them to differentiate as articular cartilage under the influence of Wnt signaling emanating from the interzone. Through experiments conducted in both chick and mouse embryos we have developed a model explaining simultaneous growth and differentiation of transient and articular cartilage in juxtaposed domains. [ABSTRACT FROM AUTHOR]