Selective stimulation of in vitro limb-bud chondrogenesis by retinoic acid.
Selective stimulation of in vitro limb-bud chondrogenesis by retinoic acid.
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DOI：
10.1111/j.1432-0436.1988.tb00087.x
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发表时间：
1988-12
期刊：
影响因子：
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通讯作者：
D. Paulsen;R. Langille;V. Dress;M. Solursh
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文献类型：
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作者：
D. Paulsen;R. Langille;V. Dress;M. Solursh
胚胎暴露于药理剂量的维生素A类似物（类维生素A）是肢体骨骼缺失、肢体截断和其他骨骼畸形的众所周知的原因。维甲酸（RA）对标准含血清培养的肢芽间充质细胞中软骨形成的唯一抑制作用同样是众所周知的，并提供了一种手段来探索RA介导的骨骼致畸作用的细胞基础。最近的研究表明，较低的RA浓度可以导致骨骼复制时，直接施加到一个发展中的肢体的前边缘，表明RA可能有一个角色，在正常的肢体发育作为一个可扩散的形态，能够调节骨骼模式。虽然RA治疗导致两者，但骨骼缺失和复制是明显不同的（如果不是相反的话）效果，后者难以与RA迄今为止对体外软骨形成的唯一抑制作用相协调。在本研究中。在鸡肢芽间充质细胞的无血清培养物中检查RA对软骨形成和肌形成的影响，并将其与在含血清培养基中生长的类似培养物的影响进行比较。当添加到无血清培养基中时，已知在体内引起骨骼复制的RA浓度显著增强体外软骨形成（超过对照值的200%），这是通过阿尔西安蓝染色和[35S]硫酸盐掺入来判断的，而对肌生成几乎没有影响。较高浓度抑制软骨形成和肌形成。结果表明，在生理浓度下。RA可以选择性地调节软骨形成的表达，并表明在较高浓度下，RA的抑制作用是不太具体的。（250字处删节）
Embryonic exposure to pharmacologic doses of vitamin A analogs (retinoids) is a well-known cause of limb-skeletal deletions, limb truncation and other skeletal malformations. The exclusively inhibitory effect of retinoic acid (RA) on chondrogenesis in standard serum-containing cultures of limb-bud mesenchymal cells is equally well known and has provided a means to explore the cellular basis for RA-mediated skeletal teratogenesis. Recent studies showing that lower RA concentrations can cause skeletal duplication when applied directly to the anterior border of a developing limb, suggest that RA may have a role in normal limb development as a diffusible morphogen capable of regulating skeletal pattern. While RA treatment causes both, skeletal deletions and duplications are clearly different (if not opposing) effects, the latter of which is difficult to reconcile with RA's heretofore exclusively inhibitory effect on in vitro chondrogenesis. In the present study. RA's effects on chondrogenesis and myogenesis were examined in serum-free cultures of chick limb-bud mesenchymal cells and compared with its effects on similar cultures grown in serum-containing medium. When added to serum-free medium, concentrations of RA known to cause skeletal duplication in vivo dramatically enhanced in vitro chondrogenesis (to over 200% of control values) as judged by both Alcian-blue staining and [35S]sulfate incorporation, while having little effect on myogenesis. Higher concentrations inhibited both chondrogenesis and myogenesis. The results indicate that at physiological concentrations. RA can selectively modulate chondrogenic expression and suggest that at higher concentrations, RA's inhibitory effects are less specific.(ABSTRACT TRUNCATED AT 250 WORDS)