Zhang Minjie, Mani Sriniwasan B, He Yao, Hall Amber M, Xu Lin, Li Yefu, Zurakowski David, Jay Gregory D, Warman Matthew L
J Clin Invest. 2016 Aug 1;126(8):2893-902. doi: 10.1172/JCI83676. Epub 2016 Jul 18.
Joints that have degenerated as a result of aging or injury contain dead chondrocytes and damaged cartilage. Some studies have suggested that chondrocyte death precedes cartilage damage, but how the loss of chondrocytes affects cartilage integrity is not clear. In this study, we examined whether chondrocyte death undermines cartilage integrity in aging and injury using a rapid 3D confocal cartilage imaging technique coupled with standard histology. We induced autonomous expression of diphtheria toxin to kill articular surface chondrocytes in mice and determined that chondrocyte death did not lead to cartilage damage. Moreover, cartilage damage after surgical destabilization of the medial meniscus of the knee was increased in mice with intact chondrocytes compared with animals whose chondrocytes had been killed, suggesting that chondrocyte death does not drive cartilage damage in response to injury. These data imply that chondrocyte catabolism, not death, contributes to articular cartilage damage following injury. Therefore, therapies targeted at reducing the catabolic phenotype may protect against degenerative joint disease.
由于衰老或损伤而退化的关节含有死亡的软骨细胞和受损的软骨。一些研究表明软骨细胞死亡先于软骨损伤，但软骨细胞的丧失如何影响软骨完整性尚不清楚。在本研究中，我们使用快速三维共聚焦软骨成像技术结合标准组织学方法，研究软骨细胞死亡是否会破坏衰老和损伤状态下的软骨完整性。我们诱导小鼠关节表面软骨细胞自主表达白喉毒素以将其杀死，并确定软骨细胞死亡不会导致软骨损伤。此外，与软骨细胞已被杀死的动物相比，膝关节内侧半月板手术失稳后，软骨细胞完整的小鼠软骨损伤增加，这表明软骨细胞死亡不会引发损伤后的软骨损伤。这些数据表明，软骨细胞分解代谢而非死亡，是损伤后关节软骨损伤的原因。因此，旨在减少分解代谢表型的疗法可能预防退行性关节疾病。
