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

Abstract

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.

Effects of SGLT2 inhibitor on tumor‐releasing chemokines/cytokines in Hep3B and Huh7 cells

“…AMPK is known to inhibit the various chemokine expressions 9 . Furthermore, mitochondrial dysfunction is reported to regulate the M‐CSF level 10 . Accordingly, SGLT2i may affect mitochondria in HCC cells and modulate the expression of several chemokines/cytokines.…”

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

“…Also, a recent study has demonstrated that H 2 S donor GYY4137 significantly relieves the inhibitory effects of dexamethasone on bone formation by activating Wnt signaling [ 30 ]. Accordingly, sodium hydrosulfide (NaHS), a donor for H 2 S, has also been shown to attenuate dexamethasone-induced systemic damage of bone mass and osteoblast dysfunction [ 31 ]. Treatment with NaHS normalizes plasma H 2 S and prevents osteoporotic bone loss in CBS-deficient mice by inhibiting inflammatory cytokines [ 32 , 33 ].…”

Hydrogen sulfide is a novel regulator implicated in glucocorticoids-inhibited bone formation

“…H 2 S has been identified in several tissues, including the vasculature, kidney, heart, brain, nervous system, and lung [17]. H 2 S is also involved in the acquisition and preservation of bone mass [18–20]. H 2 S controls stem cells function by regulating Ca 2+ influx through Ca 2+ channels, and deficiency of H 2 S impairs the osteogenic differentiation of the stem cells [18].…”