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

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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.