A gyermekkori disztális orsócsont törés kezelési lehetőségeinek retrospektív- és a csontgyógyulás vizsgálata állatkísérletes modellen

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with widespread occurrence in various organs and diverse effects both in the nervous system and in the periphery. PACAP is strongly expressed in the central nervous system, where it exerts several effects such as it is a central regulator of circadian rhythmic activities, plays a role in memory formation and psychiatric processes, and is involved in central feeding control. It elicits these actions by binding the G-protein-coupled receptors, PAC1- and VPAC1/2, which also bind vasoactive intestinal polypeptide (VIP). PACAP is also known to be expressed in the retina, along with its receptors (PAC1, VPAC1 and VPAC2 receptors). Numerous studies have provided evidence that the neuroprotective effects are mainly mediated by the PAC1 receptor and diverging downstream pathways upon its activation. Pituitary adenylate cyclase activating polypeptide is an evolutionary well conserved neuropeptide identified in hypothalamo-hypophyseal system. Two biological active forms, PACAP 1-38 and PACAP 1-27 exist with a short half-life in vivo. Since its isolation several peripheral organs have been proven to secrete and release the neuropeptide. PACAP plays a regulatory role in the development of gonads, chondrogenesis and teeth. PACAP has three main G protein coupled receptors; PAC1, VPAC1 and VPAC2 which induce the activation of adenylate cyclase, increase the intracellular cAMP concentration and can trigger the increase of PKA phosphorylation activity. Downstream target of this kinase classically can be the CREB transcription factor or in osteoblasts a possible target is the Runx2. However, it has been published that PACAP has various signalling crosstalks, for example, it has direct connection with the BMP, WNT, hedgehog or β-catenin signalling. Although PACAP has been proven to be preventive against different harmful effects, little is known about its function in bone regeneration processes.