Background: Osteoporosis has become a serious public health problem especially in postmenopausal women. This work aims to assess both the function and mechanism of SDH5 in osteoporosis.
Methods: The animal model of osteoporosis in Sprague-Dawley rats was established by utilizing ovariectomy (OVX). The trabecular bone morphometry had been determined by micro-CT, and tibia injury of rats was detected through HE and alcian blue staining. Meanwhile, the levels of oxidative stress factors, including malondialdehyde, catalase, glutathione peroxidase (GSH-Px), and superoxide (SOD), were detected by ELISA. The proliferation and apoptosis of osteoblasts isolated from OVX-induced rats were found out by CCK-8 and flow cytometry, respectively. The expression of SDH5, Osterix, Type I collagen (CoL1A1), osteocalcin (OC), SOD1, SOD2, p-MyD88/MyD88, and p-NF-κB p65/NF-κB p65 was assessed by Western blot. The effect and mechanism of SDH5 knockdown on osteoporosis were verified by lipopolysaccharide treatment.
Results: In the osteoporosis rat model, the expression of SDH5 had an up-regulated tend. A higher bone mineral density value was found in the SDH5 knockdown group. SDH5 inhibition ameliorated bone loss, mitigated bone histopathological injury, alleviated oxidative stress, and elevated osteogenic marker protein expression in vivo and in vitro. SDH5 down-regulation also promoted the proliferation and restrained apoptosis of osteoblasts extracted from OVX-induced rats. Furthermore, we found that the underlying mechanism was associated with the inhibition of the MyD88/NF-κB pathway.
Conclusion: Down-regulation of SDH5 mitigates the damage of osteoporosis both in vivo and in vitro via inhibiting the MyD88/NF-κB signaling activation.
Keywords: MyD88/NF-κB signaling; Osteoporosis; SDH5; osteoblast; oxidative stress.