Cystathionine gamma lyase-H 2 S contributes to osteoclastogenesis during bone remodeling induced by mechanical loading.

Hydrogen sulfide (H2 S), a gaseous signaling molecule produced by cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), influences bone remodeling in many ways. Osteoclasts play an important role in bone remodeling during tooth movement induced by mechanical loading, which increases the rate of tooth movement. Recently, we found that osteoclasts could produce H2 S. However, whether H2 S modulates bone remodeling by affecting osteoclasts remains unclear. In this study, we found that CSE-H2 S was a dominant H2 S generating system in osteoclasts, while CBS did not generate H2 S. A significant increase in CSE mRNA expression and H2 S production was observed in periodontal ligament (PDL) tissues of wild-type (WT) mice after 3 days of mechanical loading. CSE gene knockout led to a significant reduction in the number of maxillary osteoclasts and in the amount of tooth movement. The number of RANKL-induced TRAP-positive osteoclasts and the mRNA expression of osteoclast markers were downregulated after 6 days of incubation in monocytes extracted from CSE-/- mice. The expression of IL-1, IL-6 and TNF-α, which can stimulate osteoclastogenesis in periodontal tissue and serum samples, was lower in CSE-/- mice after mechanical loading. Application of the H2 S donor GYY4137 increased the number of RANKL-induced osteoclasts, the number of osteoclasts in periodontal tissues and tooth movement distance in CSE-/- mice. The results suggested that endogenous H2 S and CSE play vital roles in the osteoclastogenesis and alveolar bone resorption induced by mechanical loading.