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Biochemical, Genetic, and Molecular Interactions in Development - part 5

Trong một loạt các nghiên cứu trước đây từ phòng thí nghiệm của chúng tôi (Ref. 16 refs trong đó.), Chúng tôi đã cung cấp bằng chứng rằng retinoic tín hiệu thúc đẩy sự phát triển của sụn chưa trưởng thành vào chondrocytes phì đại trong ống nghiệm. Chúng tôi thấy rằng sau khi khởi phát chuyển bởi retinoids | 162 Pacifici et al. of Patched in perichondrial cells surrounding IHH-expressing prehypertrophic chondrocytes seen in long bone anlagen in vivo 5 6 10 . That is IHH produced by the prehypertrophic chondrocytes may diffuse into the perichondrium where it would trigger Patched gene expression as well as osteogenic cell differentiation and bone collar formation as our model shown in Fig. 6 prescribes . As pointed out above our data and conclusions are supported by the very recent report that in IHH-null mice there is no ossification in the limb 10 . NEED FOR RETINOID SIGNALING IN ENDOCHONDRAL OSSIFICATION In a series of previous studies from our laboratory ref. 16 and refs. therein we had provided evidence that retinoic signaling promotes the development of immature chondrocytes into hypertrophic chondrocytes in vitro. We found that upon induction by retinoids the cells progress to the terminal stage of maturation and closely resemble the posthypertrophic cells present at the chondro-osseous border in the growth plate in vivo. The phenotypic traits expressed by the retinoid-induced chondrocytes include a very large cell diameter production of mineralization-competent matrix vesicles ability to deposit apatitic crystals and high alkaline phosphatase activity. Because all these traits are actually needed for the transition from mineralized hypertrophic cartilage to endochondral bone our data suggested that by inducing such traits retinoid signaling may be required for cartilage-to-bone transition in vivo. Thus we conducted additional studies to obtain evidence in support of this important conclusion these studies have been reported 8 and only key findings are shown here. In a first set of experiments we asked whether expression of retinoid nuclear receptors is upregu-lated in prehypertrophic and or hypertrophic chondrocytes. We reasoned that such upregulation may be necessary for retinoids to act on those cells and promote terminal maturation into mineralizing .