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

Area of Science:

• Biochemistry
• Cell Biology
• Physiology

Background:

• Hydrogen sulfide (H2S) is a gasotransmitter regulating physiological functions.
• Imbalances in H2S metabolism are linked to defective bone homeostasis.
• The precise role of H2S in osteoclast differentiation is not fully understood.

Purpose of the Study:

• To investigate the effect of the H2S donor GYY4137 on osteoclast differentiation and multi-nucleation.
• To elucidate the underlying molecular mechanisms of H2S action in osteoclasts.

Main Methods:

• Osteoclast differentiation was induced using receptor activator of nuclear factor kappa-B ligand (RANKL).
• GYY4137 treatment was applied to assess its impact on osteoclast markers.
• Gene expression of osteoclast-related and cell-cell fusion molecules was analyzed.
• Mitogen-activated protein kinases (MAPKs) phosphorylation was examined.

Main Results:

• GYY4137 significantly reduced the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts.
• The expression of key osteoclast genes (NFATc1, Cathepsin K) was inhibited by GYY4137.
• GYY4137 attenuated the RANKL-induced expression of cell-cell fusion molecules (DC-STAMP, OC-STAMP, Atp6v0d2).
• GYY4137 suppressed the phosphorylation of ERK1/2, JNK1/2, and p38MAPK.

Conclusions:

• The H2S donor GYY4137 acts as a novel inhibitor of osteoclast genesis.
• GYY4137 decreases osteoclast differentiation and multi-nucleation.
• This inhibition is mediated by suppressing cell-cell fusion molecules and MAPK signaling pathways.