This study aimed to probe into the effect of TRIM33 on oxidative stress-induced apoptosis of osteoblasts in osteoporosis and to probe into the underlying mechanism. The apoptosis of osteoblasts was induced by H2 O2 treatment and tested by flow cytometry. A mouse osteoporosis model was conducted by ovariectomy (OVX). The function of TRIM33 was assessed by in vitro and in vivo experiments. The mechanism of TRIM33 was determined by immunoprecipitation, immunofluorescent staining and co-transfection experiments. Here, we found that TRIM33 expression was lessened in the osteoblasts of patients with osteoporosis and was positively correlated with the bone mineral density of these patients. FOXO3a and TRIM33 were co-localized in the osteoblasts nuclei. TRIM33 silence boosted FOXO3a degradation in normal osteoblasts, while TRIM33 overexpression restrained FOXO3a degradation in H2 O2 -treated osteoblasts. The binding of TRIM33 to CBP and its overexpression restrained CBP-mediated FOXO3a acetylation, thereby attenuating FOXO3a ubiquitylation. The H2 O2 -induced apoptosis of osteoblasts was restrained by TRIM33 overexpression, while the FOXO3a knockdown reversed this trend. The in vivo experiments corroborated that TRIM33 overexpression attenuated the OVX-driven impacts in mice. In general, our findings expounded that TRIM33 protected osteoblasts against oxidative stress-induced apoptosis in osteoporosis and that the underlying mechanism was the restraint of FOXO3a ubiquitylation and degradation.
Keywords: FOXO3a; TRIM33; apoptosis; degradation; osteoblasts.
© 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.