Induced superficial chondrocyte death reduces catabolic cartilage damage in murine posttraumatic osteoarthritis.
Induced superficial chondrocyte death reduces catabolic cartilage damage in murine posttraumatic osteoarthritis.
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DOI：
10.1172/jci83676
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发表时间：
2016-08
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通讯作者：
Minjie Zhang;Sriniwasan B. Mani;Y. He;A. Hall;Lin Xu;Yefu Li;D. Zurakowski;G. Jay;M. Warman
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作者：
Minjie Zhang;Sriniwasan B. Mani;Y. He;A. Hall;Lin Xu;Yefu Li;D. Zurakowski;G. Jay;M. Warman
由于老化或损伤而退化的关节包含死亡的软骨细胞和受损的软骨。一些研究认为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。在这项研究中，我们使用快速3D共聚焦软骨成像技术结合标准组织学检查了软骨细胞死亡是否会在衰老和损伤中破坏软骨完整性。我们诱导白喉毒素的自主表达来杀死小鼠关节表面的软骨细胞，并确定软骨细胞死亡不会导致软骨损伤。此外，在膝关节内侧半月板手术失稳后，与软骨细胞被杀死的小鼠相比，软骨细胞完整的小鼠的软骨损伤增加，这表明软骨细胞死亡并不会导致软骨损伤。这些数据表明，损伤后的关节软骨损伤是由软骨细胞分解代谢而非死亡造成的。因此，针对减少分解代谢表型的治疗可以预防退行性关节疾病。
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.