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

• Published in: Molecular biology reports 2022-07, Vol.49 (7), p.6459-6466
• Main Authors: Wu, Guanyin, Xue, Pengfei, Jin, Huricha, Zhang, Mo, Gui, Chao, Bao, Guofeng, Xu, Guanhua, Jiang, Jiawei, Zhang, Jinlong, Cui, Shengyu, Cui, Zhiming, Sun, Yuyu
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animal Anatomy; Animal Biochemistry; Apoptosis; Arthritis; Biomedical and Life Sciences; Cartilage; Cartilage diseases; Caspase-3; Chondrocytes; Collagen (type II); Collagenase 3; Degeneration; Flow cytometry; Histology; IL-1β; Immunofluorescence; Immunohistochemistry; Injection; Life Sciences; Localization; Low back pain; Matrix metalloproteinase; Metalloproteinase; Morphology; Original Article; Osteoarthritis; Signal transduction; Western blotting
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-022-07467-1

Lumbar facet osteoarthritis (FJOA) is a major cause of severe lower back pain and disability worldwide. However, the mechanism underlying cartilage degeneration in FJOA remains unclear. The purpose of this study was to investigate the regulation and mechanism of P2Y12 on chondrocyte apoptosis in FJOA. The experimental rats were randomly divided into non-operation (n = 20) and operation groups (n = 20). In the operation group, Sodium iodoacetate (MIA, Sigma, 200 mg/mL) was injected into the right L4/5 facet process using a blunt nanoneedle 26 (WPI, Sarasota, FL, USA) under the control of an injection pump. The final injection volume was 5µL and the injection rate was 2µL/min. The facet joint was removed four weeks after surgery. After the operation, samples were stored at -80 °C until further use, whereby the right facet joints in each group were tested. Hematoxylin and eosin (HE) and iron-red solid green staining were used to observe the degeneration of articular chondrocytes in rats. Immunohistochemistry and western blotting were used to observe the expressions of P2Y12, Matrix metalloproteinase 13 (MMP13), Collagen II (COL2), and other cartilage degeneration and apoptosis-related genes. Co-localization of P2Y12-cleaved caspase-3 in the apoptosis model was detected by dual-standard immunofluorescence staining. Apoptosis was also detected by flow cytometry and TUNEL assay.P2Y12 is highly expressed in OA cartilage tissue, and inhibits IL-1β -induced chondrocyte apoptosis through PI3K/AKT signaling pathway, thus playing a certain protective role on cartilage.