Hydrogen sulfide is a novel regulator implicated in glucocorticoids-inhibited bone formation
Hydrogen sulfide is a novel regulator implicated in glucocorticoids-inhibited bone formation
复制标题
硫化氢是一种新型调节剂，与糖皮质激素抑制骨形成有关
DOI：
10.18632/aging.102269
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发表时间：
2019-09-30
期刊：
影响因子：
5.2
通讯作者：
Ye, Tianwen
中科院分区：
文献类型：
--
作者：
Ma, Jun;Shi, Changgui;Ye, Tianwen
糖皮质激素会增加继发性骨质疏松症的发病率。硫化氢（H2S）是一种气体递质，在骨代谢中发挥重要作用。在这项研究中，我们研究了 H2S 对糖皮质激素诱导的骨质疏松症 (GIO) 的治疗作用。我们发现地塞米松 (Dex) 降低了血清 H2S 和体内骨髓中两种关键的 H2S 生成酶：胱硫醚 b-合酶和胱硫醚 g-裂解酶。大鼠体内 H2S 供体 GYY4137 的治疗显着缓解了 Dex 对骨形成的抑制作用。 Dex 抑制成骨细胞增殖和成骨分化，并降低两种 H2S 生成酶的表达。进一步研究表明H2S参与Dex介导的成骨细胞增殖、分化和凋亡。从机制上讲，GYY4137 通过增加 Wnt 配体的产生来激活 Wnt 信号传导，从而促进成骨细胞生成。相比之下，Wnt/β-catenin信号通路的阻断显着减轻了H2S对成骨细胞的影响。总之，恢复 H2S 水平是 GIO 的一种潜在的新型治疗方法。
Glucocorticoids contribute to the increased incidence of secondary osteoporosis. Hydrogen sulfide (H2S) is a gasotransmitter and plays an essential role in bone metabolism. In this study, we investigated the therapeutic effects of H2S on glucocorticoid-induced osteoporosis (GIO). We found that dexamethasone (Dex) decreased serum H2S and two key H2S-generating enzymes in the bone marrow in vivo, cystathione b-synthase and cystathione g-lyase. Treatment of H2S-donor GYY4137 in rat significantly relieved the inhibitory effect of Dex on bone formation. Dex inhibited osteoblasts proliferation and osteogenic differentiation and decreased the expressions of the two H2S-generating enzymes. Further investigation showed that H2S was involved in Dex-mediated osteoblasts proliferation, differentiation, and apoptosis. Mechanistically, GYY4137 promoted osteoblastogenesis by activating Wnt signaling through increased production of the Wnt ligands. In comparison, the blockage of Wnt/β-catenin signaling pathway significantly alleviated the effect of H2S on osteoblasts. In conclusion, the restoration of H2S levels is a potential novel therapeutic approach for GIO.