Campbell M A, Handley C J
Arch Biochem Biophys. 1987 Mar;253(2):462-74. doi: 10.1016/0003-9861(87)90200-1.
The addition of retinoic acid to adult bovine articular cartilage cultures produces a concentration-dependent decrease in both proteoglycan synthesis and the proteoglycan content of the tissue. Total protein synthesis was not affected by the presence of retinoic acid, indicating that the inhibition of proteoglycan synthesis was not due to cytotoxicity. The proteoglycans synthesized in the presence of retinoic acid were similar in hydrodynamic size, ability to form aggregates with hyaluronate, and glycosaminoglycan composition to those of control cultures. However, the presence of larger glycosaminoglycan chains suggests that the core protein was substituted with fewer but longer glycosaminoglycan chains. In cultures maintained with retinoic acid, a decreased ratio of the large proteoglycan was synthesized relative to the small proteoglycan compared to that measured in control cultures. In cultures maintained with retinoic acid for 1 day and then switched to medium with 20% (v/v) fetal calf serum, the rate of proteoglycan synthesis and hexuronate contents increased within 5 days to levels near those of control cultures. Within 2 days of switching to medium with 20% (v/v) fetal calf serum, the relative proportions of the proteoglycan species were similar to those produced in cultures maintained in medium with 20% (v/v) fetal calf serum throughout. The rate of proteoglycan synthesis by bovine articular cartilage cultures exhibited an exponential decay following exposure to retinoic acid, with estimated half-lives of 11.5 and 5.3 h for tissue previously maintained in medium alone or containing 20% (v/v) fetal calf serum, respectively. The addition of 1 mM benzyl beta-D-xyloside only partially reversed the retinoic acid-mediated inhibition of proteoglycan synthesis. This indicates that the inhibition of proteoglycan synthesis by retinoic acid was due to both a decreased availability of xylosylated core protein and a decreased capacity of the chondrocytes to synthesize chondroitin sulfate chains.
向成年牛关节软骨培养物中添加视黄酸会导致蛋白聚糖合成及组织中蛋白聚糖含量呈浓度依赖性降低。视黄酸的存在并不影响总蛋白合成，这表明蛋白聚糖合成的抑制并非由细胞毒性所致。在视黄酸存在的情况下合成的蛋白聚糖，其流体力学大小、与透明质酸形成聚集体的能力以及糖胺聚糖组成与对照培养物中的相似。然而，存在较大的糖胺聚糖链表明核心蛋白被较少但更长的糖胺聚糖链所取代。在添加视黄酸的培养物中，与对照培养物相比，大蛋白聚糖相对于小蛋白聚糖的合成比例降低。在添加视黄酸培养1天然后换成含20%（v/v）胎牛血清的培养基的培养物中，蛋白聚糖合成速率和己糖醛酸含量在5天内增加到接近对照培养物的水平。换成含20%（v/v）胎牛血清的培养基后2天内，蛋白聚糖种类的相对比例与全程在含20%（v/v）胎牛血清的培养基中培养所产生的相似。牛关节软骨培养物中蛋白聚糖的合成速率在接触视黄酸后呈指数衰减，对于先前仅在培养基中或含20%（v/v）胎牛血清的培养基中培养的组织，估计半衰期分别为11.5小时和5.3小时。添加1 mM苄基β-D-木糖苷仅部分逆转了视黄酸介导的蛋白聚糖合成抑制。这表明视黄酸对蛋白聚糖合成的抑制是由于木糖基化核心蛋白的可用性降低以及软骨细胞合成硫酸软骨素链的能力下降。
