Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia.
J Cell Biochem. 2013 Feb;114(2):245-9. doi: 10.1002/jcb.24362.
Osteoarthritis is characterized by degenerative alterations of articular cartilage including both the degradation of extracellular matrix and the death of chondrocytes. The PI3K/Akt pathway has been demonstrated to involve in both processes. Inhibition of its downstream target NF-kB reduces the degradation of extracellular matrix via decreased production of matrix metalloproteinases while inhibition of mTOR increased autophagy to reduce chondrocyte death. However, mTOR feedback inhibits the activity of the PI3K/Akt pathway and inhibition of mTOR could result in increased activity of the PI3K/Akt/NF-kB pathway. We proposed that the use of dual inhibitors of PI3K and mTOR could be a promising approach to more efficiently inhibit the PI3K/Akt pathway than rapamycin or PI3K inhibitor alone and produce better treatment outcome.
骨关节炎的特征是关节软骨发生退行性改变，包括细胞外基质的降解和软骨细胞的死亡。PI3K/Akt 通路已被证明参与这两个过程。抑制其下游靶点 NF-κB 通过减少基质金属蛋白酶的产生来减少细胞外基质的降解，而抑制 mTOR 则通过增加自噬来减少软骨细胞的死亡。然而，mTOR 反馈抑制 PI3K/Akt 通路的活性，抑制 mTOR 可能导致 PI3K/Akt/NF-κB 通路活性增加。我们提出，使用 PI3K 和 mTOR 的双重抑制剂可能是一种很有前途的方法，比雷帕霉素或单独的 PI3K 抑制剂更有效地抑制 PI3K/Akt 通路，并产生更好的治疗效果。
