Fasudil Ameliorates Osteoporosis Following Myocardial Infarction by Regulating Cardiac Calcitonin Secretion.

We hypothesis that Rho kinase inhibitor fasudil ameliorates osteoporosis following myocardial infarction (MI) by regulating cardiac calcitonin secretion. A mice model of MI and cultured neonatal cardiomyocytes exposed to hypoxia and serum deprivation (H/SD), and fibroblasts exposed to TGF-ß were used, respectively. Cardiac function in vivo was assessed with echocardiography. Osteoporosis in vivo was assessed with X-ray and micro-CT. In vivo and in vitro studies used histological and immunohistochemical techniques, along with western blots. In mice post-MI, fasudil ameliorates the microstructure and bone metabolism of the lumbar, improved cardiac function, and attenuated myocardial fibrosis. In vitro, fasudil or αCGRP could effectively inhibit the proliferation of primary fibroblasts treated with TGF-ß. Moreover, fasudil ameliorates the cardiac calcitonin secretion induced by MI in vivo or by H/SD in vitro. Our findings suggest that fasudil improved MI-induced osteoporosis by promoting cardiac secreting calcitonin.

Inhibition of carrageenan-induced dental inflammatory responses owing to decreased TRPV1 activity by Dexmedetomidine.

BACKGROUND: Dexmedetomidine (Dex) is a highly selective agonist of the α2 adrenergic receptor and a common sedative; however, its anti-inflammatory effect has been studied. In this study, the inhibitory effect of Dex on inflammation in dental pulp cells was assessed. For this, the effect of Dex on inflammation induced by carrageenan (Car) in human dental pulp cells (hDPCs) was evaluated. Car incubation induced a robust inflammatory response in hDPCs as well as activation of PKA-STAT3 and PKC-nuclear factor kappa B (NF-κB) signaling pathways. RESULTS: Dex reduced the expression of inflammatory cytokines in a dose-dependent manner. Meanwhile, the phosphorylation of PKA, PKC, STAT3, and NF-κB as well as the nuclear accumulation of STAT3 and NF-κB were significantly increased in Dex-treated Car-induced hDPCs. Western blotting results also showed that the phosphorylation level of transient receptor potential cation channel subfamily V member 1 (TRPV1) was downregulated as a result of Dex treatment. Furthermore, we found that administration of the TRPV1 agonist capsaicin (Cap) reversed the effects of Dex on proinflammatory cytokines; however, the expression and activation of PKA-STAT3 and PKC-NF-κB signals were not altered owing to Cap administration. CONCLUSIONS: These results indicate that Dex plays a defensive role in dental pulp inflammation by regulating the TRPV1 channel and can be used as a potential target for human dental pulp inflammation intervention.