Glorie Lorenzo, D'Haese Patrick C, Verhulst Anja
Laboratory of Pathophysiology, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Laboratory of Pathophysiology, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Bone. 2016 Nov;92:37-49. doi: 10.1016/j.bone.2016.08.009. Epub 2016 Aug 12.
Dipeptidyl peptidase 4 (DPP4) is a conserved exopeptidase with an important function in protein regulation. The activity of DPP4, an enzyme which can either be anchored to the plasma membrane or circulate free in the extracellular compartment, affects the glucose metabolism, cellular signaling, migration and differentiation, oxidative stress and the immune system. DPP4 is also expressed on the surface of osteoblasts, osteoclasts and osteocytes, and was found to play a role in collagen metabolism. Many substrates of DPP4 have an established role in bone metabolism, among which are incretins, gastrointestinal peptides and neuropeptides. In general, their effects favor bone formation, but some effects are complex and have not been completely elucidated. DPP4 and some of its substrates are known to interact with adipokines, playing an essential role in the energy metabolism. The prolongation of the half-life of incretins through DPP4 inhibition led to the development of these inhibitors to improve glucose tolerance in diabetes. Current literature indicates that the inhibition of DPP4 activity might also result in a beneficial effect on the bone metabolism, but the long-term effect of DPP4 inhibition on fracture outcome has not been entirely established. Diabetic as well as postmenopausal osteoporosis is associated with an increased activity of DPP4, as well as a shift in the expression levels of DPP4 substrates, their receptors, and adipokines. The interactions between these factors and their relationship in bone metabolism are therefore an interesting field of study.
二肽基肽酶4（DPP4）是一种保守的外肽酶，在蛋白质调节中具有重要作用。DPP4这种酶的活性可锚定在质膜上或在细胞外区室中游离循环，它会影响葡萄糖代谢、细胞信号传导、迁移和分化、氧化应激以及免疫系统。DPP4也表达于成骨细胞、破骨细胞和骨细胞表面，并且被发现参与胶原蛋白代谢。DPP4的许多底物在骨代谢中发挥既定作用，其中包括肠促胰岛素、胃肠肽和神经肽。总体而言，它们的作用有利于骨形成，但有些作用较为复杂且尚未完全阐明。已知DPP4及其一些底物与脂肪因子相互作用，在能量代谢中发挥重要作用。通过抑制DPP4来延长肠促胰岛素的半衰期，促使了这些抑制剂的研发，以改善糖尿病患者的糖耐量。目前的文献表明，抑制DPP4活性可能也会对骨代谢产生有益影响，但DPP4抑制对骨折结局的长期影响尚未完全明确。糖尿病性骨质疏松以及绝经后骨质疏松均与DPP4活性增加以及DPP4底物、其受体和脂肪因子的表达水平变化有关。因此，这些因素之间的相互作用及其在骨代谢中的关系是一个有趣的研究领域。
