Hydrogen sulfide regulates bone remodeling and promotes orthodontic tooth movement

Hydrogen sulfide (H2S) is a gas signaling molecule that has multiple influences on physiological and pathological processes in the mammalian body, including vasodilation, neurotransmission, inflammation, hypoxia sensing and bone remodeling. Our previous studies suggested that H2S might be involved in the periodontal tissue remodeling during the orthodontic tooth movement (OTM) via increasing periodontal ligament cell differentiation, tissue mineralization, bone formation and collagen synthesis. The aim of the present study was to investigate the effects of H2S on alveolar bone remodeling that is associated with tooth movement. Experiments were performed in an OTM mouse model. Sodium hydrosulfide (NaHS), which is a donor of H2S and DL-propargylglycine (PAG) and a cystathionine-gamma-lyase (CSE) inhibitor, which could also decrease H2S expression, were administered intra-peritoneally and respectively. A total of 60 male C57BL6/J mice were divided into 4 groups; Control, NaHS, PAG and combination (PAG+NaHS). The rate of OTM and the bone mineral density (BMD) of alveolar bone were scanned and measured by micro-computed tomography (micro-CT). The number of osteoclasts and expression of the tumor necrosis factor ligand superfamily member-11 (RANKL), alkaline phosphatase (ALP), osteocalcin (OCN) and osteoprotegerin (OPG) in alveolar bone were accessed to evaluate the osteoclastic activity and osteogenesis with histochemistry of tartrate-resistant acid phosphatase staining, immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. In the alveolar bone, NaHS increased the OTM and decreased the BMD, respectively. PAG significantly decrease OTM and increased the BMD. NaHS combined with PAG rescued the PAG-induced changes in the OTM and the BMD. Additionally, the number of osteoclasts, the expression of RANKL, ALP, OCN and the ratio of RANKL/OPG were significantly up-regulated in the NaHS group. In contrast, PAG down-regulated the number of osteoclasts, the expression of RANKL, ALP, OCN and the ratio of RANKL/OPG. These findings suggested that H2S might facilitate the OTM by enhancing alveolar bone remodeling as a result of an increased osteoclastic activity and osteogenesis.