Sodium hydrosulfide mitigates dexamethasone-induced osteoblast dysfunction by interfering with mitochondrial function.

Osteoporosis is one of the clinical complications of long-term treatment with glucocorticoids (GCs), characterized by systemic damage of bone mass and osteoblast dysfunction. Hydrogen sulfide was found to be involved in GCs-induced osteoblast dysfunction. Osteoblastic MC3T3-E1 cell and mitochondrial function were determined by cell viability, M-CSF level, and ALP activity and superoxide production, membrane potential, and ATP level, respectively. The purpose of this research was to explore the impact of NaHS on osteoblastic MC3T3-E1 cell function as well as on Sirt1 and PGC1α expression in dexamethasone (DEX)-treated osteoblast cells. DEX-treated MC3T3-E1 cells exhibited decreased cell viability and ALP activity, as well as increased M-CSF level; all these changes were dramatically attenuated by NaHS. DEX-treated cells also displayed mitochondrial dysfunction, namely decreased mitochondrial membrane potential and ATP generation and increased superoxide generation, which were partly reversed by NaHS. We confirmed decreased Sirt1 and PGC1α protein expression in DEX-treated MC3T3-E1 cells by Western blot, which was also partly reversed by NaHS. Silencing of Sirt1 abrogated the protective effect of NaHS against DEX-induced cell damage and mitochondrial dysfunction. NaHS alleviates DEX-induced osteoblastic MC3T3-E1 cell injury by improving mitochondrial function.