Exploratory study on the development of novel therapy targeting.-glutamyl transpeptidase

胆汁淤积性肝病常表现为γ-谷氨酰转肽酶（GGT）水平升高和继发性骨质疏松。GGT被认为是一种新的骨吸收因子，可刺激破骨细胞的形成。在血清GGT水平升高的BDL大鼠中，随着破骨细胞的增加，骨减少明显。这些变化被AGT 3显著减弱。体外研究显示，GGT刺激可显著上调破骨细胞通过成骨细胞的生成，并抑制成骨细胞分化。此外，牙周组织中GGT的上调可诱导牙槽骨破坏和破骨细胞生成，而抗体治疗可减少其发生。因此，通过AGT 3管理升高的GGT可能成为胆汁淤积性肝病继发性骨质疏松症和牙周炎的新治疗剂。

Cholestatic liver diseases often manifest the increased levels of γ- glutamyl transpeptidase(GGT) and secondary osteoporosis. GGT is known as a novel bone resorbing factor that stimulates osteoclast formation. The aim of this study was to elucidate the mechanisms by which GGT causes bone reduction.In BDL rats with elevation of serum GGT level, bone reduction with increase of osteoclasts was evident. These changes were significantly attenuated by AGT3. In vitro study showed significant upregulation of osteoclastogenesis via osteoblasts and inhibition of osteoblast differentiation with GGT stimulation. Moreover upregulation of GGT in periodontal tissue induced alveolar bone destruction with osteoclastogenesis, whereas antibody treatment reduced it. Therefore managing the elevated GGT by AGT3 may become a novel therapeutic agent for secondary osteoporosis and periodontitis in cholestatic liver diseases.