Upregulation of P2Y12 inhibits chondrocyte apoptosis in lumbar osteoarthritis through PI3K/AKT signaling pathway

Abstract

BackgroundLumbar facet osteoarthritis (FJOA) is one of the major causes of severe low back pain and disability worldwide. However, the underlying mechanism of cartilage degeneration in FJOA remains unclear. MethodsThe rats were randomly divided into non-operation group (n=20) and operation group (n=10). In the operation group, MIA (Sigma, 200mg/mL) was injected into the right L4/5 facet process by blunt nanoneedle 26 (WPI, Sarasota, FL, USA) under the control of injection pump. The final injection volume was 5μL and the injection rate was 2μL/min. The facet joint was removed 4 weeks after surgery. After the operation, some samples were stored at 80°C until use. The right facet joints in each group were tested as follows. HE staining and iron red solid green staining were used to observe the degeneration of articular chondrocytes in rats. Immunohistochemistry and Western blot were used to observe the expression of P2Y12, MMP13, COL2 and other cartilage degeneration and apoptosis related indexes. Co-localization of P2Y12-Cleaved caspase-3 in apoptosis models was detected by dual-standard immunofluorescence staining. Apoptosis was detected by flow cytometry and TUNEL.ResultsThe expression of P2Y12 increased in OA cartilage tissue, and P2Y12 inhibited apoptosis. Knockdown of P2Y12 promotes IL-1β -induced apoptosis.ConclusionOur data suggest that P2Y12 has a chondroprotective effect on FJOA.

Role of signal transduction pathways in IL‐1β‐induced apoptosis: Pathological and therapeutic aspects

“…In recent years, there has been increasing evidence that regulation of the cell cycle through the PI3K/Akt signaling pathway can inhibit IL-1β-induced apoptosis and inflammatory. 85,86 First, Cai et al found that compared to normal cells and tissues, apoptosis was increased in IL-1β-treated articular chondrocytes accompanied by downregulation of PI3K mRNA levels, 4 which demonstrated that PI3K is associated with apoptosis. Next, Guo et al found that 17β-estradiol attenuated IL-1β-induced early apoptosis in nucleus pulposus cells by increasing the expression of activated mechanistic target of rapamycin (mTOR) and decreasing the expression of activated caspase-3, in intervertebral disc lesions.…”

“…In recent years, there has been increasing evidence that regulation of the cell cycle through the PI3K/Akt signaling pathway can inhibit IL‐1β‐induced apoptosis and inflammatory 85,86 . First, Cai et al found that compared to normal cells and tissues, apoptosis was increased in IL‐1β‐treated articular chondrocytes accompanied by downregulation of PI3K mRNA levels, 4 which demonstrated that PI3K is associated with apoptosis.…”