Styrud J, Eriksson U J
Department of Medical Cell Biology, Uppsala University, Sweden.
Teratology. 1991 Jul;44(1):65-75. doi: 10.1002/tera.1420440111.
In human and experimental diabetic pregnancy there is an increased risk of congenital malformation in the offspring. Some malformations involve growth retardation and altered chondrocyte differentiation, suggesting that a diabetic milieu may modify embryonic cell replication and the development of (pre)chondrocytes. The aim of the present work was to study the effects of a diabetes-like environment in vitro on the growth and differentiation of rat chondrocytes in the presence of specific growth factors and different concentrations of serum. This was performed with a modified micromass culture system of embryonic (pre)chondrocytes from the limb bud and mandibular arch areas using medium supplemented with different glucose concentrations and with serum from diabetic rats. An elevated ambient glucose concentration inhibited the growth of mature chondrocytes in vitro, and this effect was diminished in a serum-rich culture milieu. The (pre)chondrocytes exhibited a marked dependence on the serum level in the culture medium for optimal in vitro development. Diabetic rat serum had the lowest stimulatory capacity of the three different types tested (at similar glucose concentrations), suggesting a deficiency of growth-stimulating factor(s) rather than the presence of inhibiting factor(s) in this type of serum. One of the deficient factor(s) in diabetic rat serum may be similar to IGF-II, but a combined deficiency of several growth-stimulating agents is likely to be present. Chondrocytes originating from the mandibular arch in general appeared more sensitive to MSA and IGF-II than those from the limb buds. The present observations support the notion that while diabetes-induced hyperglycemia in the conceptus contributes to severe growth retardation of the mandibular arch, additional factors also play a role.
在人类糖尿病妊娠及实验性糖尿病妊娠中，后代出现先天性畸形的风险增加。一些畸形涉及生长发育迟缓以及软骨细胞分化改变，这表明糖尿病环境可能会改变胚胎细胞复制以及（前）软骨细胞的发育。本研究的目的是在特定生长因子和不同浓度血清存在的情况下，研究体外类似糖尿病的环境对大鼠软骨细胞生长和分化的影响。这是通过改良的微团培养系统来进行的，该系统使用来自肢芽和下颌弓区域的胚胎（前）软骨细胞，培养基中添加了不同葡萄糖浓度以及糖尿病大鼠的血清。升高的环境葡萄糖浓度在体外抑制了成熟软骨细胞的生长，而在富含血清的培养环境中这种影响会减弱。（前）软骨细胞在体外的最佳发育对培养基中的血清水平表现出明显的依赖性。在测试的三种不同类型血清（在相似葡萄糖浓度下）中，糖尿病大鼠血清的刺激能力最低，这表明这类血清中缺乏生长刺激因子而非存在抑制因子。糖尿病大鼠血清中缺乏的因子之一可能类似于胰岛素样生长因子-II，但很可能还存在几种生长刺激剂的联合缺乏。一般来说，源自下颌弓的软骨细胞比源自肢芽的软骨细胞对促有丝分裂活性物质（MSA）和胰岛素样生长因子-II更敏感。本研究结果支持这样一种观点，即虽然胚胎中的糖尿病诱导的高血糖会导致下颌弓严重生长发育迟缓，但其他因素也起作用。
