Selenium-modified bone cement promotes osteoporotic bone defect repair in ovariectomized rats by restoring GPx1-mediated mitochondrial antioxidant functions

Abstract

Over-accumulation of reactive oxygen species (ROS) causes mitochondrial dysfunction and impairs the osteogenic potential of bone marrow-derived mesenchymal stem cells (BMMSCs). Selenium (Se) protects BMMSCs from oxidative stress-induced damage; however, it is unknown whether Se supplementation can promote the repair of osteoporotic bone defects by rescuing the impaired osteogenic potential of osteoporotic BMMSCs (OP-BMMSCs). In vitro treatment with sodium selenite (Na2SeO3) successfully improved the osteogenic differentiation of OP-BMMSCs, as demonstrated by increased matrix mineralization and up-regulated osteogenic genes expression. More importantly, Na2SeO3 restored the impaired mitochondrial functions of OP-BMMSCs, significantly up-regulated glutathione peroxidase 1 (GPx1) expression, and attenuated the intracellular ROS and mitochondrial superoxide. Silencing of Gpx1 completely abrogated the protective effects of Na2SeO3 on mitochondrial functions of OP-BMMSCs, suggesting the important role of GPx1 in protecting OP-BMMSCs from oxidative stress. We further fabricated Se-modified bone cement based on silk fibroin and calcium phosphate cement (SF/CPC). After eight weeks of implantation, Se-modified bone cement significantly promoted bone defect repair, evidenced by the increased new bone tissue formation and enhanced GPx1 expression in ovariectomized rats. These findings revealed that Se supplementation rescued mitochondrial functions of OP-BMMSCs through activation of the GPx1-mediated antioxidant pathway, and more importantly, supplementation with Se in SF/CPC accelerated bone regeneration in ovariectomized rats, representing a novel strategy for treating osteoporotic bone fractures or defects.

RNA sequencing-based approaches to identifying disulfidptosis-related diagnostic clusters and immune landscapes in osteoporosis

“…Evidence suggests that FLNA is involved in negatively regulating osteogenesis and positively modulating osteoclastogenesis [ 39 ]. Loss of NUBPL function triggers mitochondrial dysfunction [ 40 ], which could disrupt both bone formation and resorption [ 41 ]. Importantly, the present study confirmed that the disulfidptosis regulators ACTB, FLNA, and NUBPL exhibited lower expression levels in OP samples, thus influencing disulfidptosis processes in OP.…”

Zinc-energized dynamic hydrogel accelerates bone regeneration via potentiating the coupling of angiogenesis and osteogenesis

“…8-week-old male Sprague-Dawley (SD) rat BMSCs were extracted with reference to previous studies ( Zhou et al, 2023 ). Rat BMSCs were cultured using modified α-minimum medium (containing 10% fetal bovine serum, 1% penicillin, and streptomycin) at 37°C in an environment of 5% carbon dioxide.…”

Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway

“…The isolation of rat BMMSCs was conducted using 8-week-old Sprague Dawley (SD) rats in accordance with a previously reported protocol [ 22 ]. Specifically, after sacrificing, the rat femurs and tibias were collected.…”