Osteocrin, a bone-derived humoral factor, exerts a renoprotective role in ischemia-reperfusion injury in mice

Background Osteocrin (OSTN), a bone-derived humoral factor, was reported to act on heart and bone by potentiating the natriuretic peptide (NP) system. Ostn gene polymorphisms have been associated with renal function decline, but its pathophysiological role in the kidney remains unclear. Methods The role of endogenous OSTN was investigated using systemic Ostn-knockout mice (KO). As a model for OSTN administration, liver-specific Ostn-overexpressing mice crossed with KO (KO-Tg) were generated. These mice were subjected to the unilateral ischemia-reperfusion injury, and renal lesions after 21 days of insult were evaluated. A comprehensive analysis of the Wnt/β-catenin pathway was performed using a PCR array. Reporter plasmid-transfected proximal tubular cells (NRK52E) were used to investigate the mechanism by which OSTN affects the pathway. Results After injury, KO showed marginal worsening of renal fibrosis compared to wild-type mice, with comparable renal atrophy. KO-Tg showed significantly ameliorated renal atrophy, fibrosis and tubular injury, together with reduced expressions of fibrosis- and inflammation-related genes. PCR array showed that the activation of the Wnt/β-catenin pathway was attenuated in KO-Tg. The downstream targets, Mmp7, Myc, and Axin2 showed similar results. MMP7 and Wnt2 were induced in corticomedullary proximal tubules after injury, but not in KO-Tg. In NRK52E, OSTN significantly potentiated the inhibitory effects of NP on TGFβ1-induced activation of the Wnt/β-catenin pathway, which was reproduced by a cGMP analog. Conclusions Ectopic Ostn overexpression ameliorated subsequent renal injury following ischemia-reperfusion. OSTN could represent possible renoprotection in acute to chronic kidney disease transition, thus serving as a potential therapeutic strategy.

Effects of Gegen Dingxuan Capsule on behavior, X-Ray Signs of the Cervical Spine, and Humoral Factor Levels in a Rat Model of Cervical Vertigo

Objective. To investigate the effects of Gegen Dingxuan capsule on behavior, X-ray signs of the cervical spine, and levels of norepinephrine (NE), nitric oxide (NO), endothelin (ET-1), and calcitonin gene-related peptide (CGRP) in the plasma of a rat model of cervical vertigo and additionally to clarify the underlying mechanisms of action. Method. A total of 40 male SPF Sprague-Dawley rats were randomly assigned to blank control, model, Sibelium, and Gegen Dingxuan capsule groups, with 10 rats in each group. A rat model of cervical vertigo was produced by physically damaging the cervical spine, thereby perturbing its stability. After cervical spine surgery, rats in the Sibelium and Gegen Dingxuan capsule groups were administered Sibelium and Gegen Dingxuan capsule, respectively. After 4 and 8 weeks of administration, balance beam test was used to assess behavior, lateral X-ray images of the cervical spine were taken and scored, and the plasma levels of NE, NO, ET-1, and CGRP were measured. Results. After 4 and 8 weeks of drug administration, the balance beam test scores in the Gegen Dingxuan capsule group were significantly higher than those in the Sibelium group. The radiographic scores were significantly lower in the Gegen Dingxuan capsule group than those in the Sibelium group at 8 weeks. Plasma NE, NO, ET-1 levels, and ET-1/CGRP ratio were significantly decreased in the Gegen Dingxuan capsule group compared with the model group. No significant difference was found between the Sibelium and Gegen Dingxuan capsule groups. Plasma CGRP levels were significantly increased in the Gegen Dingxuan capsule group compared with the model group and were significantly decreased compared with the Sibelium group. Conclusions. Gegen Dingxuan capsule improves behavior, radiographic scores, reduces plasma levels of NE, NO, ET-1, and the ET-1/CGRP ratio, and increases plasma CGRP levels. Gegen Dingxuan capsule may improve outcome in the rat model of cervical vertigo by ameliorating cervical facet joint disorder, relieving cervical muscle spasm and vasospasm, increasing blood supply, and regulating humoral factor levels.