Kinney R C, Schwartz Z, Week K, Lotz M K, Boyan B D
Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Osteoarthritis Cartilage. 2005 Apr;13(4):330-7. doi: 10.1016/j.joca.2004.12.003.
The higher incidence of osteoarthritis in females suggests that there may be intrinsic sex-specific differences in human articular chondrocytes. 17beta-Estradiol (E2) regulates rat growth plate chondrocytes through traditional nuclear receptor mechanisms, but only female cells exhibit rapid membrane-associated effects mediated through protein kinase C (PKC) alpha. Here we demonstrate sexual dimorphism in the physiological response of human articular chondrocytes to E2.
Articular chondrocytes were obtained at the time of autopsy from three male and three female donors between 16 and 39 years of age. Second passage cultures were treated with E2 for 24 h to assess the effects of the hormone on [3H]-thymidine incorporation, [35S]-sulfate incorporation, and alkaline phosphatase specific activity. In addition, the chondrocytes were treated for 3, 9, 90 or 270 min and PKC specific activity was determined.
All chondrocytes were positive for aggrecan and estrogen receptor alpha mRNAs but were negative for type II collagen mRNA. Only cells from female donors responded to E2. DNA synthesis, sulfate incorporation and alkaline phosphatase activity were increased. E2 caused a rapid increase in PKC activity in the female cells within 9 min that was maximal at 90 min. Treatment with the PKC inhibitor chelerythrine blocked these effects.
These results provide the first definitive evidence that normal human cells exhibit an intrinsic sex-specific response to E2 and suggest that sexual dimorphism may be an important variable in assessing the pathways that modulate cell behavior.
骨关节炎在女性中的发病率较高，这表明人类关节软骨细胞可能存在内在的性别特异性差异。17β-雌二醇（E2）通过传统的核受体机制调节大鼠生长板软骨细胞，但只有雌性细胞表现出通过蛋白激酶C（PKC）α介导的快速膜相关效应。在此，我们证明了人类关节软骨细胞对E2的生理反应存在性别二态性。
在尸检时从3名年龄在16至39岁之间的男性和3名女性供体获取关节软骨细胞。对第二代培养物用E2处理24小时，以评估该激素对[3H]-胸腺嘧啶核苷掺入、[35S]-硫酸盐掺入和碱性磷酸酶比活性的影响。此外，对软骨细胞处理3、9、90或270分钟，并测定PKC比活性。
所有软骨细胞的聚集蛋白聚糖和雌激素受体α mRNA均呈阳性，但II型胶原mRNA呈阴性。只有来自女性供体的细胞对E2有反应。DNA合成、硫酸盐掺入和碱性磷酸酶活性增加。E2在9分钟内使雌性细胞中的PKC活性迅速增加，在90分钟时达到最大值。用PKC抑制剂白屈菜红碱处理可阻断这些效应。
这些结果提供了首个确凿证据，即正常人类细胞对E2表现出内在的性别特异性反应，并表明性别二态性可能是评估调节细胞行为途径时的一个重要变量。
