Reddi A H
Centre for Tissue Regeneration and Repair, Department of Orthopaedic Surgery, University of California, Davis School of Medicine, Sacramento, California 95817, USA.
Ann Rheum Dis. 2003 Nov;62 Suppl 2(Suppl 2):ii73-8. doi: 10.1136/ard.62.suppl_2.ii73.
Articular cartilage homoeostasis is critical for joint function. The steady state homoeostasis of articular cartilage is a balance between anabolic morphogens such as cartilage derived morphogenetic proteins (CDMPs) and bone morphogenetic proteins (BMPs) of the BMP family and catabolic cytokines such as interleukin (IL)1, IL17, and tumour necrosis factor alpha. Although bone and articular cartilage are adjacent tissues, there is a profound difference in their regeneration potential. Bone has the highest potential for regeneration. On the other hand, articular cartilage is recalcitrant to repair.
To examine the hypothesis that the feeble innate regeneration ability of cartilage is due to the preponderance of catabolic cytokines such as IL1 and IL17.
During a systematic investigation of CDMPs and cytokines IL17B (chondroleukin) was found in bovine articular cartilage.
BMP-7 and IL17B are present in articular cartilage and synthesised in chondrocytes as shown by northern blots and real-time reverse transcription-polymerase chain reaction. The coexistence of anabolic morphogens and catabolic cytokines in articular cartilage has important implications for cartilage homoeostasis and regeneration. The networks of signalling systems of morphogens and cytokines determine the net capacity for regenerative morphogenesis of articular cartilage. Finally, the feeble innate capacity for articular cartilage may be improved by targeted therapy by soluble receptors to block catabolic cytokines.
关节软骨的稳态对于关节功能至关重要。关节软骨的稳态是一种平衡,一方面是合成代谢形态发生素,如软骨衍生形态发生蛋白(CDMPs)和骨形态发生蛋白(BMP)家族中的骨形态发生蛋白,另一方面是分解代谢细胞因子,如白细胞介素(IL)-1、IL-17和肿瘤坏死因子α。尽管骨和关节软骨是相邻组织,但它们的再生潜力存在显著差异。骨具有最高的再生潜力。另一方面,关节软骨难以修复。
检验软骨先天再生能力微弱是由于IL-1和IL-17等分解代谢细胞因子占优势这一假说。
在对CDMPs和细胞因子进行系统研究期间,在牛关节软骨中发现了IL-17B(软骨白细胞介素)。
如Northern印迹法和实时逆转录-聚合酶链反应所示,BMP-7和IL-17B存在于关节软骨中,并由软骨细胞合成。合成代谢形态发生素和分解代谢细胞因子在关节软骨中的共存对软骨稳态和再生具有重要意义。形态发生素和细胞因子的信号系统网络决定了关节软骨再生形态发生的净能力。最后,通过可溶性受体进行靶向治疗以阻断分解代谢细胞因子,可能会改善关节软骨先天的微弱能力。