Different Susceptibilities of Osteoclasts and Osteoblasts to Glucocorticoid-Induced Oxidative Stress and Mitochondrial Alterations

Abstract

Glucocorticoid-induced bone loss is the most common form of secondary osteoporosis. This toxic effect has not been efficiently managed, possibly due to the incomplete understanding of the extraordinarily diverse cellular responses induced by glucocorticoid treatment. Previous literatures revealed that high dose of exogenous glucocorticoid triggers apoptosis in osteocytes and osteoblasts. This cell death is associated with glucocorticoid-induced oxidative stress. In this study, we aimed to investigate the mechanisms of glucocorticoid-induced apoptosis in osteoblasts and examine the responses of osteoclasts to the synthetic glucocorticoid, dexamethasone. We demonstrated the biphasic effects of exogenous glucocorticoid on osteoblastic mitochondrial functions and elevated intracellular oxidative stress in a dose- and time-dependent manner. On comparison, similar treatment did not induce mitochondrial dysfunctions and oxidative stress in osteoclasts. The production of reactive oxygen/nitrogen species was decreased in osteoclasts. The differences are not due to varying efficiency of cellular antioxidant system. The opposite effects on nitrogen oxide synthase might provide an explanation, as the expression levels of nos2 gene are suppressed in the osteoclast but elevated in the osteoblast. We further revealed that glucocorticoids have a substantial impact on the osteoblastic mitochondria. Basal respiration rate and ATP production were increased upon 24 h incubation of glucocorticoids. The increase in proton leak and nonmitochondrial respiration suggests a potential source of glucocorticoid-induced oxidative stress. Long-term incubation of glucocorticoids accumulates these detrimental changes and results in cytochrome C release and mitochondrial breakdown, consequently leading to apoptosis in osteoblasts. The mitochondrial alterations might be other sources of glucocorticoid-induced oxidative stress in osteoblasts.

Association of Hydrogen Sulfide with Femoral Bone Mineral Density in Osteoporosis Patients: A Preliminary Study

“…This turnover is precisely controlled by bone-resorbing osteoclasts and osteocytes, as well as bone-forming osteoblasts [ 11 , 12 ]. Activation of osteoclasts and inactivation of osteoblasts synergistically contribute to the development and progression of various bone diseases, including osteoporosis [ 13 , 14 ]. Therefore, current treatment regimens for osteoporosis fall into 2 categories: antiresorptive drugs, such as estrogen-receptor analogs or bisphosphonates, that inhibit osteoclast function, and anabolic drugs, namely parathyroid hormone, that induce osteoblastic bone formation.…”

Identification and analysis of mitochondria-related central genes in steroid-induced osteonecrosis of the femoral head, along with drug prediction

“…Some studies have indicated that increasing the activity of SOD can help counteract the progression of femoral head necrosis in the context of apoptosis mediated by the Bcl-2 protein family. Therefore, SOD and SQOR may hold significant value in inhibiting the progression of femoral head necrosis ( 75 ), requiring further exploration. Research has shown a close relationship between the Nrf2 pathway and the FTH1 gene.…”

Investigating the Differential Circulating microRNA Expression in Adolescent Females with Severe Idiopathic Scoliosis: A Proof-of-Concept Observational Clinical Study

“…Oxidative stress is a primary contributor to orthopedic ailments, including osteoarthritis and osteoporosis. The stress interferes with bone remodeling and increases the likelihood of fractures [ 79 , 80 ]. Severe muscle injury and accumulated oxidative stress increased in idiopathic scoliosis compared to HC [ 81 ].…”