Peroxiredoxin6 Promotes Osteogenic Differentiation And Bone Formation By Reducing Cellular Senescence Through The CAMP/PKA/CREB Pathway

BackgroundPeroxiredoxin6(PRDX6)is an antioxidant enzyme in the PRX family that attenuates oxidative stress injury by reducing intracellular ROS levels.Appropriate amounts of ROS are physiologically required,but oxidative stress caused by excessive ROS can lead to osteoblast senescence followed by reduced osteoblast differentiation function,ultimately causing abnormal bone formation and leading to osteoporosis.OBJECTIVESThe aim of this study was to investigate the effect and mechanism of PRDX6 on osteoblast senescence induced by oxidative stress in osteoporosis.METHODSThe levels of PRDX6 and bone mineral density(BMD)in the blood of patients with clinically normal and osteoporosis were collected and measured and correlated.The PRDX6 gene was knocked down or overexpressed in MC3T3-E1 cells by lentiviral infection,and the osteogenesis-related pathways and osteogenic function changes were observed under oxidative stress.The ovariectomy-induced osteoporosis model was established,and the recombinant adeno-associated virus(rAAV-PRDX6)was specifically overexpressed by intra-articular injection to observe the bone mass and related pathway protein expression changes in the model mice.RESULTSThe expression of PRDX6 in the serum of patients with osteoporosis decreased,which was positively correlated with the degree of BMD.In vitro experiments have shown that knockdown of PRDX6 can lead to increased ROS levels,increased senescence-related manifestations(increased expression of senescence-related phenotypic products,cell cycle arrest,etc.),decreased activity,and decreased osteoblast function in osteoblasts stimulated by oxidative stress.PRDX6 overexpression,on the other hand,alleviates the performance.In vivo results showed that overexpression of PRDX6 reduced senescence-related protein expression and significantly alleviated the degree of osteopenia in osteoblasts in castrated mice compared with controls.CONCLUSIONPRDX6 alleviates osteoporotic changes by inhibiting oxidative stress-induced aging in osteoblasts...