Gumi Bao decoction regulates bone metabolism-related mRNA expression in glucocorticoid-induced osteoporosis in rats.

BACKGROUND: Gumi Bao decoction is effective for the treatment of osteoporosis, but the theoretical and scientific basis is unknown. This study aimed to observe the effect of Gumi Bao decoction on Dickkopf-related protein 1 (DKK1) mRNA, runt-related transcription factor 2 (Runx2) mRNA, and cathepsin K (CTSK) mRNA in glucocorticoid-induced osteoporosis (GIOP) in rats and to investigate the underlying mechanism. METHODS: Sixty Sprague-Dawley (SD) rats were weighed and randomly divided into six groups: the normal control group (NC group), the methylprednisolone group (Met group), the Fosamax group, the low-dose Gumi Bao Decoction group (GBDL group), the medium-dose Gumi Bao Decoction group (GBDM group), and the high-dose Gumi Bao Decoction group (GBDH group). The basic physiological conditions of the rats and the bone morphology of the fourth lumbar vertebra and the left femur of three rats in each group were observed, and the mRNA expressions of bone tissue-related genes were detected. RESULTS: After administration, DKK1 mRNA expression was significantly up-regulated in the Met group compared to the NC group (P<0.001). Meanwhile, DKK1 mRNA was significantly down-regulated in the Fosamax group compared with the Met group (P<0.001). There was a significant difference in the down-regulation of DKK1 mRNA between the GBDM and GBDH groups (P<0.001). Runx2 mRNA was considerably down-regulated in the Met group compared with the NC group (P<0.001). Runx2 mRNA was up-regulated in the GBDM group, and the GBDH group was significantly different compared to the Met group (P<0.001). CTSK mRNA was significantly up-regulated in the Met group compared to the NC group (P<0.001). Compared with the Met group, CTSK mRNA expression was significantly down-regulated in the Fosamax group (P<0.001), as well as in the GBDL, GBDM, and GBDH groups (P<0.001). At 200× and 400×, there were significantly fewer osteoblasts and osteoclasts in the Met group than in the Fosamax, GBDM, and GBDH groups. CONCLUSIONS: The imbalance of bone homeostasis of GIOP is caused by an increase in bone resorption and decreased osteogenesis. Gumi Bao could regulate bone metabolism through the action of DKK1 via the Wnt/ß-catenin signaling pathway, up-regulating Runx2 mRNA and down-regulating CTSK mRNA.

Therapeutic effect of Resveratrol in the treatment of osteoarthritis via the MALAT1/miR-9/NF-κB signaling pathway.

The aim of the current study was to explore the role of Resveratrol (Res) in osteoarthritis (OA) and its underlying mechanism. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to determine the relative expression levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), microRNA-9 (miR-9), nuclear factor kappa B subunit 1 (NF-κB1), interleukin (IL)-6, matrix metallopeptidase 13 (MMP-13) and caspase-3 in vitro and in the in vivo model of OA, as well as examining the effect of Res on MALAT1, miR-9 and NF-κB1, IL-6, MMP-13 and caspase-3 expression levels. Immunohistochemical analysis was performed to examine NF-κB1 and MMP-13 protein levels in the in vivo model of OA. Dual-luciferase reporter assays were used to confirm the regulatory relationship between miR-9 and MALAT1 and NF-κB1, as well as examining the effect of Res on the transcriptional activation of MALAT1 promoter. Furthermore, the effect of Res on cell proliferation in vitro was examined by MTT assay. The relative mRNA expression levels of MALAT1 and NF-κB1 were significantly increased, while miR-9 expression was significantly decreased in the OA group compared with the sham group. Treatment with Res partially reversed the effects of OA on MALAT1, NF-κB1 and miR-9 expression. Similarly, the relative protein expression levels of NF-κB1, IL-6, MMP-13 and caspase-3 were significantly increased in the OA group compared with the sham group; however, treatment with Res partially reversed the effects of OA on the protein expression levels of NF-κB1, IL-6, MMP-13 and caspase-3. MALAT1 and NF-κB1 were identified as potential target genes of miR-9, and dual-luciferase assays were used to examine the effect of miR-9 on the luciferase activity of 3'UTR MALAT1 and NF-κB1. Treatment with Res suppressed the transcriptional activation of the MALAT1 promoter, thereby inhibiting MALAT1 expression. Additionally, the relative expression level of miR-9 significantly increased following treatment with Res in a dose-dependent manner, while the relative protein expression levels of NF-κB1, IL-6, MMP-13 and caspase-3 significantly decreased following treatment with Res compared with the control. Furthermore, treatment with Res significantly increased the growth rate of chondrocytes in a dose-dependent manner compared with the control. Taken together, these results suggest that direct targeting of the MALAT1/miR-9/NF-κB1/IL-6, MMP-13/caspase-3 axis may be a novel therapeutic strategy for the treatment of OA.

Comparison studies of the Scheimpflug lidar technique and the pulsed lidar technique for atmospheric aerosol sensing.

The Scheimpflug lidar (SLidar) technique has been recently developed for various remote sensing applications, where the lidar signal is detected by an image sensor according to the Scheimpflug principle instead of the time-of-flight principle. Comparison studies between the SLidar technique and the conventional pulsed lidar technique are crucial for understanding the principle as well as the measurement results of the SLidar technique. In this work, a 520-nm Scheimpflug lidar system and a 532-nm pulsed lidar system have been developed for comparison studies. Atmospheric remote measurements as well as statistical analysis have been carried out on a near-horizontal path and on a slant direction with an elevation angle of 30$^\circ $∘. The temporal-spatial variations of the atmospheric backscattering maps measured by the 520-nm SLidar system and the 532-nm pulsed lidar system generally agreed well. The median extinction coefficient measured by the SLidar and the pulsed techniques has shown similar temporal evolution during the near-horizontal comparison study, and a correlation coefficient of 0.99 has been achieved through statistical analysis on all lidar measurements. Moreover, the root-mean-square error (RMSE) ratio for each extinction coefficient profile has also been evaluated, and the mean value of the RMSE ratio for all lidar measurements was about 11% in homogeneous atmospheric conditions. During slant comparison studies, the RMSE ratio between the SLidar curve and the pulsed lidar curve was less than 5% in the region of 0.5-2 km, and it generally increased with the increase of measurement distance, primarily due to the decreased range resolution of the SLidar technique. The promising results suggested that the SLidar technique, featuring a short blind range, could be suitable for aerosol sensing, particularly in the planetary boundary layer.

Detection of the planetary boundary layer height by employing the Scheimpflug lidar technique and the covariance wavelet transform method.

A portable Scheimpflug lidar system has been employed for atmospheric boundary layer studies. Atmospheric backscattering signals were continuously recorded from 21 August to 28 August 2018. The covariance wavelet transform (CWT) method was utilized to identify the maximum gradient of recorded lidar curves as the planetary boundary layer (PBL) height. As the directly retrieved PBL height could be underestimated or overestimated due to the presence of residual layers and thin clouds, localized atmospheric turbulence, aerosol stratification, etc., a CWT-based quality-control algorithm has also been developed to improve the reliability of the PBL height retrieval. The temporal distribution of the final PBL height has shown a clear diurnal variation as the ambient temperature changed due to the increasing and decreasing of surface heating during a one-week continuous measurement campaign. The promising results have shown great potential in employing the Scheimpflug lidar technique and the CWT-based method in the determination of the PBL height.

(2R,3S)-Pinobanksin-3-cinnamate promotes osteoblast differentiation through cAMP and cGMP pathways

Abstract Flavones have the potential of being used as a dietary supplement for bone health promotion beyond calcium and vitamin D. Recent studies have showed that flavones enhanced bone formation and inhibited bone resorption by affecting osteoblast and osteoclast differentiation through various cell signaling pathways. In this study, we investigated the effects of a new flavone (2R,3S)-pinobanksin-3-cinnamate, isolated from the metabolites of the endophytic fungus Penicillium sp. FJ-1 of Acanthus ilicifolius L., Acanthaceae, on osteoblast differentiation by using MC3T3-E1 cells. It was observed that (2R,3S)-pinobanksin-3-cinnamate promoted osteoblast differentiation, as evidenced by increased mineralization process and alkaline phosphatase activity, as well as expression of genes encoding the bone differentiation. Moreover (2R,3S)-pinobanksin-3-cinnamate treatment upregulated the gene expression of wingless-type MMTV integration site family, bone morphogenetic protein and runt-related transcription factor 2, and protein expression of phosphor-Smad1/5/8, β-catenin and runt-related transcription factor 2 in MC3T3-E1 cells. The osteoblast differentiation effects induced by (2R,3S)-pinobanksin-3-cinnamate were attenuated by the bone morphogenetic protein antagonist Noggin, and wingless-type MMTV integration site family signaling pathway inhibitors Dickkopf-1. Co-treatment with adenosine 30,50-cyclic monophosphate and guanosine 30,50-cyclic monophosphate pathway inhibitors, H89 and KT5823, respectively, reversed the (2R,3S)-pinobanksin-3-cinnamate-induced activations of p-Smad1/5/8, β-catenin, and runt-related transcription factor 2. Our data demonstrated that (2R,3S)-pinobanksin-3-cinnamate promoted the osteoblast differentiation of MC3T3-E1 cells, at least partially through the adenosine 30,50-cyclic monophosphate and guanosine 30,50-cyclic monophosphate signaling pathways, providing the scientific rational to develop (2R,3S)-pinobanksin-3-cinnamate against bone loss-associated diseases.