Langille R M, Paulsen D F, Solursh M
Department of Biology, University of Iowa, Iowa City 52242.
Differentiation. 1989 May;40(2):84-92. doi: 10.1111/j.1432-0436.1989.tb00817.x.
Recent studies have shown that in the developing limb bud retinoic acid is a skeletal morphogen at physiological levels, but a potent teratogen at higher levels. Retinoic acid has also been shown to be teratogenic during facial development, but very low levels may have an as yet unspecified role in normal development. In the present study the effects of retinoic acid on chondrogenesis and myogenesis by craniofacial cells grown in micromass cell culture were investigated. Retinoic acid, at concentrations of 0.01-100 ng/ml, was supplied to cells derived from day-4 (H.H stage 23/24) chick embryo mandibular, maxillary and frontonasal processes, grown in micromass cultures for 4 days in both serum-containing and defined media. Based on Alcian-blue-staining, concentrations of retinoic acid of 0.1-1 ng/ml were found to enhance chondrogenesis by mandibular cells grown in defined medium, while greater concentrations up to 100 ng/ml inhibited chondrogenesis. By contrast, chondrogenesis was generally retarded by all concentrations of retinoic acid applied to frontonasal cells grown in defined medium and when applied to both mandibular and frontonasal cells when grown in serum-containing medium. Cells from stage-23/24 maxillae did not display any significant chondrogenic activity in either medium under these culture conditions. Unlike chondrogenesis, myogenesis in mandibular, frontonasal and maxillary cultures was greater in defined than serum-containing medium, based on the appearance of immunologically detectable muscle myosin, and was reduced considerably less in defined medium by all concentrations of retinoic acid tested. In the presence of serum however, myogenesis was retarded with increasing concentrations of retinoic acid beyond 1 ng/ml in micromass cultures from all three facial regions.(ABSTRACT TRUNCATED AT 250 WORDS)
最近的研究表明，在发育中的肢芽中，视黄酸在生理水平上是一种骨骼形态发生原，但在较高水平时是一种强效致畸剂。视黄酸在面部发育过程中也被证明具有致畸性，但极低水平可能在正常发育中发挥尚未明确的作用。在本研究中，研究了视黄酸对在微团细胞培养中生长的颅面细胞软骨生成和肌生成的影响。将浓度为0.01 - 100 ng/ml的视黄酸添加到源自第4天（哈氏分期23/24）鸡胚下颌、上颌和额鼻突的细胞中，这些细胞在含血清和限定培养基中进行微团培养4天。基于阿尔辛蓝染色，发现0.1 - 1 ng/ml的视黄酸浓度可增强在限定培养基中生长的下颌细胞的软骨生成，而高达100 ng/ml的更高浓度则抑制软骨生成。相比之下，应用于在限定培养基中生长的额鼻细胞的所有视黄酸浓度，以及应用于在含血清培养基中生长的下颌和额鼻细胞时，软骨生成通常都会受到抑制。在这些培养条件下，来自23/24期上颌的细胞在两种培养基中均未表现出任何显著的软骨生成活性。与软骨生成不同，基于免疫可检测的肌肉肌球蛋白的出现，下颌、额鼻和上颌培养物中的肌生成在限定培养基中比在含血清培养基中更强，并且在限定培养基中，所有测试浓度的视黄酸对肌生成的抑制作用要小得多。然而，在有血清存在的情况下，在来自所有三个面部区域的微团培养物中，当视黄酸浓度超过1 ng/ml时，肌生成会随着浓度增加而受到抑制。（摘要截选至250字）
