Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization.

Alveolar bone regeneration has been strongly linked to macrophage polarization. M1 macrophages aggravate alveolar bone loss, whereas M2 macrophages reverse this process. Berberine (BBR), a natural alkaloid isolated and refined from Chinese medicinal plants, has shown therapeutic effects in treating metabolic disorders. In this study, we first discovered that culture supernatant (CS) collected from BBR-treated human bone marrow mesenchymal stem cells (HBMSCs) ameliorated periodontal alveolar bone loss. CS from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in vitro. To clarify the underlying mechanism, the bioactive materials were applied to different animal models. We discovered macrophage colony-stimulating factor (M-CSF), which regulates macrophage polarization and promotes bone formation, a key macromolecule in the CS. Injection of pure M-CSF attenuated experimental periodontal alveolar bone loss in rats. Colony-stimulating factor 1 receptor (CSF1R) inhibitor or anti-human M-CSF (M-CSF neutralizing antibody, Nab) abolished the therapeutic effects of the CS of BBR-treated HBMSCs. Moreover, AKT phosphorylation in macrophages was activated by the CS, and the AKT activator reversed the negative effect of the CSF1R inhibitor or Nab. These results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT axis. Further studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction sockets. Overall, our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.

Orexin: a potential role in the process of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a complicated disease with an unrecognized mechanism. Obesity, sex, age, and smoking have been found to be independent correlates of OSA. Orexin (also named hypocretin) mainly secreted by lateral hypothalamus neurons has a wide array of biological functions like regulating sleep, energy levels and breathing. Several clinical studies found ties between orexin and OSA. Because of the close correlation between orexin and obesity, sex, age and smoking (which are the key risk factors for OSA patients), we hypothesize that orexin may play a key role in the pathogenesis of OSA.

Influence of hypercapnia on the synthesis of neuropeptides and their receptors in murine brain.

BACKGROUND AND OBJECTIVE: Sleep disorders are a complicated and major public health concern affecting millions of individuals. Obstructive sleep apnoea (OSA) is a common but still under-recognized disease which can cause intermittent nocturnal hypercapnia. Neuropeptides play critical roles in neurotransmission, acting as transmitters or modulators. Results from recent studies have implicated several neuropeptides in sleep and breathing regulation, including orexin, neuropeptides Y and galanin. Therefore, the present study aimed to evaluate the influence of hypercapnia on these neuropeptides and their receptors in order to assess their potential role in the pathogenesis of OSA. METHODS: Fifteen C57BL/6J mice were randomly divided into three groups and exposed to moderate hypercapnia (5% CO(2) with balanced room air), or severe hypercapnia (10% CO(2) with balanced room air) or room air for 3 h (9:00-12:00 h), respectively. Immediately following exposure the brainstem and hypothalamus were excised for real-time reverse transcription polymerase chain reaction and western blot analyses. RESULTS: In the hypothalamus gene expression including galanin, orexin and neuropeptide Y receptor 1 (NPYR1) was downregulated by hypercapnia. However, protein and mRNA levels of orexin-A receptor were upregulated by severe hypercapnia. In the brainstem only NPYR1 mRNA expression was decreased in moderate hypercapnia compared with that in severe hypercapnia. CONCLUSIONS: These findings suggest that hypercapnia can affect these neuropeptides and their receptors, especially the orexin and orexin-A receptor. The potential relationships between these peptides and OSA are worthy of further investigation.