This study explored the potential mechanism of SIRT1 in bovine osteoarthritis (OA). In vivo experiments evaluated the severity of damage to bovine tarsal cartilage tissue through pathological staining and Mankin scoring. When compared with healthy bovines, cartilage in OA-affected bovines displayed ECM degradation and increased Mankin scores (P<0.01). In the cartilage of OA-affected cattle, the protein expression of inflammatory factors (TNF-α, IL-1β, COX-2) and ECM degradation markers (MMP-3, MMP-13) was increased (P<0.05), the expression levels of key pathway proteins (including SIRT1, nuclear Nrf2 and HO-1) were decreased (P<0.05), and the expression of nuclear p65 and p-IκBα was upregulated (P<0.05). In vitro studies, we developed a bovine primary chondrocyte inflammation model using 10ng/mL IL-1β. IL-1β treatment significantly upregulated the expression levels of ECM degradation markers in chondrocytes (P<0.01). Transmission electron microscopy revealed mitochondrial ultrastructural damage, and flow cytometry indicated an apoptosis rate of 38.1%. ML334 treatment significantly enhanced the levels of nuclear Nrf2, HO-1, and Bcl-2 (P<0.05), while simultaneously decreasing nuclear p65, BAX, Cleaved caspase-3, and ECM degradation markers (P<0.05). JSH-23 treatment successfully downregulated nuclear p65 and ECM degradation marker levels (P<0.05). Treatment with the SIRT1 agonist SRT2104 not only increased the level of SIRT1, nuclear Nrf2, and HO-1 (P<0.05), but also effectively attenuated the expression of nuclear p65 (P<0.05). This experiment strongly supports the claim that SIRT1 effectively protects bovine cartilage ECM from degradation and apoptosis through a dual mechanism of action (activation of the Nrf2/HO-1 pathway and inhibition of the NF-κB pathway).

To Cite This Article: Qiu Z, Qi J, Guo X, Gao T, Bai H, Wei C, Zhang Z, Li Y, Ma Y, Zhang J and Ma T, 2026. SIRT1 inhibits bovine cartilage ECM degradation and apoptosis by activating Nrf2/HO-1 and inhibiting NF-κB pathways. Pak Vet J, 46(2): 460-467. http://dx.doi.org/10.29261/pakvetj/2026.034