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内容記述 |
Lysyl hydroxylase 2 (LH2), encoded by the procollagen lysine 2-oxoglutarate 5-dioxygenase 2 (Plod2) gene, catalyzes the hydroxylation of lysine residues in the fibrillar collagen telopeptides. This post-translational modification is essential for forming the stable hydroxylysine-aldehyde derived collagen cross-links that play a critical role in collagen stability, mechanical strength, and bone formation. Defective LH2 activities have been implicated in bone disorders including Bruck syndrome, however, effective agents that control LH2 activity have not been developed until now. In this study, using in silico docking simulations, we identified a small molecule (KS122-0485428) that specifically binds LH2, and assessed the effects of this compound on collagen cross-linking, cell proliferation, and mineralization using the murine osteoblastic cell line MC3T3-E1. While KS122-0485428 did not affect cell proliferation and LH2 expression, it significantly accelerated mineralization. The hydroxylysine-aldehyde derived collagen cross-links were also significantly increased at the expense of the lysine-aldehyde derived cross-link. These results demonstrate that KS122-0485428 enhances LH2 activity leading to accelerated mineralization. Thus, this novel LH2 activator has the potential as a therapeutic agent for bone repair and regeneration. |
