Héraud F, Héraud A, Harmand M F
INSERM U443, Victor Segalen University, Bordeaux, France.
Ann Rheum Dis. 2000 Dec;59(12):959-65. doi: 10.1136/ard.59.12.959.
To investigate whether apoptosis occurs in osteoarthritis (OA), and if this phenomenon is modulated by human recombinant interleukin 1beta (hrIL1beta).
Human articular cartilage samples were obtained at the time of hip arthroplasty because of femoral neck fracture (normal cartilage) (n=4) or advanced coxarthrosis (OA cartilage) (n=14). Apoptotic chondrocytes, isolated by collagenase digestion and cultivated for 24 hours, or present in situ in frozen cartilage sections, were quantified by fluorescent microscopy using two apoptosis markers: the TUNEL reaction, which detects nuclear DNA fragmentation, and Annexin-V-fluos, which labels at the membrane level the externalisation of phosphatidylserine.
In OA cartilage 18-21% of chondrocytes showed apoptotic features, compared with 2-5% in normal cartilage. The results were similar for the two comparative studies (in situ and in vitro) and for both apoptosis markers. Moreover, hrIL1beta increased the apoptosis rate in vitro in a dose dependent manner in OA and normal chondrocytes.
These results suggest that apoptosis may be an important factor in the evolution of OA and may be a new target for treatment of OA.
研究骨关节炎(OA)中是否发生细胞凋亡,以及这种现象是否受重组人白细胞介素1β(hrIL1β)调节。
因股骨颈骨折行髋关节置换术时获取人关节软骨样本(正常软骨)(n = 4)或晚期髋关节炎(OA软骨)(n = 14)。通过胶原酶消化分离并培养24小时的凋亡软骨细胞,或冷冻软骨切片中原位存在的凋亡软骨细胞,使用两种凋亡标记物通过荧光显微镜进行定量:检测核DNA片段化的TUNEL反应,以及在膜水平标记磷脂酰丝氨酸外化的膜联蛋白V-荧光素。
在OA软骨中,18% - 21%的软骨细胞呈现凋亡特征,而正常软骨中这一比例为2% - 5%。两种比较研究(原位和体外)以及两种凋亡标记物的结果相似。此外,hrIL1β在体外以剂量依赖方式增加OA和正常软骨细胞的凋亡率。
这些结果表明,细胞凋亡可能是OA进展中的一个重要因素,可能是OA治疗的新靶点。