2022, Vol. 26 ›› Issue (20): 3147-3151

Relationship between apoptosis of osteoarthritis chondrocytes and reduction of histone deacetylase 4 content

Gu Xiaodong1, Li Fei2, Che Xianda2, Li Pengcui2   

Abstract: BACKGROUND: Endoplasmic reticulum stress-mediated chondrocyte apoptosis plays an important role in the pathogenesis of osteoarthritis, which is mainly regulated by the activated transcription factor 4 (ATF4)/CAAT/enhancer-binding protein homologous protein (CHOP) signaling pathway. However, the mechanism of this signaling pathway in osteoarthritis remains unclear.
OBJECTIVE: To investigate the mechanism of histone deacetylase 4 and ATF4/CHOP signaling pathway in osteoarthritis chondrocytes apoptosis.
METHODS: According to Outerbridge classification, the articular cartilage of the tibial plateau cartilage obtained during knee joint replacement was divided into relatively normal cartilage (Outerbridge I) and osteoarthritis cartilage (Outerbridge III). Apoptosis of chondrocytes was observed by TUNEL staining. Immunohistochemistry staining was used to detect the expression of histone deacetylase 4, ATF4, and CHOP. Real-time fluorescence quantitative PCR was used to detect the mRNA expression of CHOP, while western blot and real-time fluorescence quantitative PCR were used to detect the protein expression of histone deacetylase 4 and ATF4.
RESULTS AND CONCLUSION: TUNEL staining results showed that the apoptosis rate of chondrocytes in osteoarthritic cartilage was higher than that in relatively normal cartilage [(83.5±10.1)% vs. (20.5±5.2)%, P < 0.05]. Immunohistochemical staining results showed that the expression of ATF4 in osteoarthritic cartilage was significantly higher than that in relatively normal cartilage, and the expression of histone deacetylase 4 in osteoarthritic cartilage was lower than that in relatively normal cartilage. The expression of CHOP in osteoarthritis cartilage was higher than that in relatively normal cartilage. The mRNA expression of ATF4 and CHOP in osteoarthritic cartilage were higher than that in relative normal cartilage (P < 0.05), and the mRNA expression of histone deacetylase 4 in osteoarthritic cartilage was lower than that in relative normal cartilage (P < 0.05). The protein expression of histone deacetylase 4 in osteoarthritic cartilage was lower than that in relatively normal cartilage (P < 0.05), and the protein expression of ATF4 in osteoarthritic cartilage was higher than that in relatively normal cartilage (P < 0.05). Therefore, in the pathological process of osteoarthritis, the downregulated expression of histone deacetylase 4 and upregulated expression of ATF4/CHOP signal pathway molecules may be related to chondrocyte apoptosis in osteoarthritis.
Key words: osteoarthritis, chondrocyte, histone deacetylase 4, activating transcription factor 4, CAAT/enhancer binding protein homologous protein, endoplasmic reticulum stress, apoptosis