Yang C, Li S W, Helminen H J, Khillan J S, Bao Y, Prockop D J
Department of Biochemistry and Molecular Biology, Jefferson Institute of Molecular Medicine, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Exp Cell Res. 1997 Sep 15;235(2):370-3. doi: 10.1006/excr.1997.3692.
Previous work demonstrated that collagen fibrils were not detectable in the cartilage of transgenic mice homozygous for targeted inactivation of the collagen II gene. In the present work, we used the same mice to show that chondrocytes undergo apoptosis in the absence of collagen II, the major component of the extracellular matrix of cartilage. The chondrocytes in the homozygous mice had condensed nuclei, fragmentation of nuclear DNA, and decreased levels of the Bcl-2 protein. These results provide direct evidence that cartilage extracellular matrix lacking collagen II cannot support the survival of chondrocytes. In addition, the results suggest that apoptosis may play a role in degenerative connective tissue diseases such as osteoarthritis in which there is extensive tissue loss.
先前的研究表明，在胶原II基因靶向失活的纯合转基因小鼠的软骨中，无法检测到胶原纤维。在本研究中，我们使用同样的小鼠来证明，在缺乏软骨细胞外基质主要成分胶原II的情况下，软骨细胞会发生凋亡。纯合小鼠的软骨细胞出现核浓缩、核DNA片段化以及Bcl-2蛋白水平降低。这些结果提供了直接证据，表明缺乏胶原II的软骨细胞外基质无法支持软骨细胞的存活。此外，这些结果表明，细胞凋亡可能在诸如骨关节炎等存在广泛组织损失的退行性结缔组织疾病中起作用。
