Functional analysis of endoplasmic reticulum stress in the progression of cartilage degeneration

我们利用Chop-基因敲除(Chop-/-)的软骨细胞和手术诱导的小鼠骨关节炎(OA)模型，研究了促凋亡转录因子Chop在小鼠软骨细胞凋亡和软骨退变过程中的作用。我们的结果表明，CHOP在软骨细胞的凋亡中起直接作用，内质网(ER)应激介导的细胞凋亡参与了小鼠软骨退变的进程。我们还利用Perk+/-、Ire1pha+/-和Atf6pha-/-小鼠模型和这些基因敲除的软骨细胞，研究了ER应力传感器PERK、Ire1α和Atf6α在软骨退行性变和软骨细胞代谢中的作用。结果提示，Atf6α参与了软骨退变的过程，Ire1α和Atf6α的表达与软骨细胞合成代谢有关。

We investigated the role of proapoptotic transcription factor Chop in murine chondrocyte apoptosis and in the progression of cartilage degeneration, using Chop-knockout (Chop-/-) chondrocytes and model of surgically-induced osteoarthritis (OA) in Chop-/- mice. Our results indicate that Chop plays a direct role in chondrocyte apoptosis and that endoplasmic reticulum (ER) stress-mediated apoptosis contributes to the progression of cartilage degeneration in mice. We also investigated the role of ER stress sensor Perk, Ire1alpha, and Atf6alpha in cartilage degeneration and chondrocyte metabolism with Perk+/-, Ire1alpha+/-, and Atf6alpha-/- mouse models of OA and these genes-knockdown chondrocytes. The results suggest that Atf6alpha involves the progress of cartilage degeneration and the expression of Ire1alpha and Atf6alpha relates with chondrocyte anabolism.