Hydrogen sulfide donor GYY4137 attenuates RANKL-induced osteoclast differentiation and multi-nucleation

Hydrogen sulfide (H₂S) is a novel gasotransmitter produced in mammalian cells and is known to various regulate physiological functions. Previous study reported that an imbalance in H₂S metabolism is associated with defective bone homeostasis. However, the detailed mechanism of how H₂S affect osteoclast differentiation remains unclear. In the present study, we demonstrated that the effect of H₂S donor GYY4137 on osteoclast differentiation and multi-nucleation. Treatment of GYY4137 significantly decreased the number of receptor activator of nuclear factor kappa-B ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive cells and inhibited the expression of osteoclast-related genes, nuclear factor of activated T-cells 1 (NFATc1) and Cathepsin K(Ctsk). Additionally, the increased gene expression of dendritic cell-specific transmembrane protein (DC-STAMP), osteoclast stimulatory transmembrane protein (OC-STAMP), and v-ATPase V0 subunit d2 (Atp6v0d2), which are cell-cell fusion-related molecules by RANKL treatment, was attenuated by GYY4137. Furthermore, GYY4137 suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK1/2, and p38MAPK, compared to RANKL-treated cells. Thus, our data suggested that H₂S donor GYY4137 as a novel osteoclast genesis inhibitor, significantly decreases osteoclast differentiation and multi-nucleation by inhibiting the expression of the cell-cell fusion molecules.