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.