Oroxin B alleviates osteoarthritis through anti-inflammation and inhibition of PI3K/AKT/mTOR signaling pathway and enhancement of autophagy.

Background: Osteoarthritis (OA) is a common aging-related degenerative joint disease with chronic inflammation as its possible pathogenesis. Oroxin B (OB), a flavonoid isolated from traditional Chinese herbal medicine, possesses anti-inflammation properties which may be involved in regulating the pathogenesis of OA, but its mechanism has not been elucidated. Our study was the first to explore the potential chondroprotective effect and elucidate the underlying mechanism of OB in OA. Methods: In vitro, primary mice chondrocytes were stimulated with IL-1ß along with or without the administration of OB or autophagy inhibitor 3-methyladenine (3-MA). Cell viability assay was measured with a cell counting kit-8 (CCK-8). The phenotypes of anabolic-related (Aggrecan and Collagen II), catabolic-related (MMP3, MMP13, and ADAMTS5), inflammation-related (iNOS, COX-2, TNF-α, IL-6, and IL-1ß), and markers of related signaling pathways in chondrocytes with different treatment were detected through western blot, RT-qPCR, and immunofluorescent staining. In vivo, the destabilized medial meniscus (DMM) operation was performed to establish the OA mice model. After knee intra-articular injection with OB for 8 weeks, the mice's knee joints were obtained for subsequent histological staining and analysis. Results: OB reversed the expression level of anabolic-related proteins (Aggrecan and Collagen II) and catabolic-related (MMP3, MMP13, and ADAMTS5) in IL-1ß-induced chondrocytes. Mechanistically, OB suppressed the inflammatory response stimulated by IL-1ß, as the inflammation-related (iNOS, COX-2, TNF-α, IL-6, and IL-1ß) markers were downregulated after the administration of OB in IL-1ß-induced chondrocytes. Besides, the activation of PI3K/AKT/mTOR signaling pathway induced by IL-1ß could be inhibited by OB. Additionally, the autophagy process impaired by IL-1ß could be rescued by OB. What's more, the introduction of 3-MA to specifically inhibit the autophagic process impairs the protective effect of OB on cartilage. In vivo, histological staining revealed that intra-articular injection of OB attenuated the cartilage degradation, as well as reversed the expression level of anabolic and catabolic-related proteins such as Aggrecan, Collagen II, and MMP13 induced in DMM-induced OA models. Conclusions: The study verified that OB exhibited the chondroprotective effect by anti-inflammatory, inhibiting the PI3K/AKT/mTOR signaling pathway, and enhancing the autophagy process, indicating that OB might be a promising agent for the treatment of OA.

Association between polymorphisms in vitamin D receptor gene and adolescent idiopathic scoliosis: a meta-analysis.

PURPOSE: This meta-analysis was performed to clarify whether the two single nucleotide polymorphisms (ApaI and BsmI) in vitamin D receptor (VDR) gene conferred susceptibility to adolescent idiopathic scoliosis (AIS). METHODS: A comprehensive literature search in five online databases (PubMed, EMBASE, ISI Web of Science, CNKI, and Wanfang) was performed to identify studies that analyzed the association between VDR gene polymorphisms and risk of AIS. Observational studies met the predetermined inclusion criteria were selected for meta-analysis. The most appropriate genetic model was identified using a genetic model-free approach. Meta-analysis was performed using RevMan 5.3 software. RESULTS: Five eligible studies were included in this meta-analysis, which involved a total of 717 cases and 554 controls. A statistically significant association was observed between BsmI polymorphism and AIS (OR 1.90, 95% CI 1.32, 2.62). In subgroup analysis by ethnicity, the association between BsmI polymorphism and AIS was significant in Asians (OR 2.06, 95% CI 1.56, 2.73) but not in Caucasians (OR 0.70, 95% CI 0.23, 2.19). However, the ApaI polymorphism was not associated with AIS. Moreover, no evidence of association between BMD and the two VDR gene polymorphisms was detected. CONCLUSIONS: Meta-analysis of existing data suggested that BsmI was associated with increased risk of AIS in Asian populations. Nevertheless, further studies with rigorous design and more ethnic groups are encouraged to validate our findings. These slides can be retrieved under Electronic Supplementary Material.

Update on the Clinical Effect of Acupuncture Therapy in Patients with Gouty Arthritis: Systematic Review and Meta-Analysis.

Objective. The aim of this study is to evaluate the clinical efficacy and safety of acupuncture therapy in the treatment of acute gouty arthritis. Methods. A literature search of PubMed, EMBASE, ISI Web of Science, CENTRAL, and CNKI was conducted from the inception date of each database up to October 2015. Two investigators screened each article independently and were blinded to the findings of the other reviewer. Data was extracted according to the predetermined collection form. Meta-analysis was performed. Results. We analyzed data from 28 RCTs involving 2237 patients with gouty arthritis. Compared with conventional pharmacological treatments acupuncture was more effective in rendering patients free from symptoms after 24 hours, lowering serum urate, alleviating pain associated with gouty arthritis, and decreasing the ESR; regarding CRP, no statistically significant difference was found. In addition, the frequency of adverse events in acupuncture treatment was lower than that in control group. Conclusion. Based on the findings of our study, we cautiously suggest that acupuncture is an effective and safe therapy for patients with gouty arthritis. However, the potential beneficial effect of acupuncture might be overstated due to the methodological deficiency of included studies. High quality RCTs with larger scale are encouraged.

Icariine Restores LPS-Induced Bone Loss by Downregulating miR-34c Level.

Bacteria-induced inflammatory responses cause excessive bone resorption in chronic inflammatory diseases such as septic arthritis, osteomyelitis, and orthopedic implant failure. Icariine has been reported to facilitate the bone healing and reduce the occurrence of osteoporosis in clinical, moreover, laboratory studies which have proved that Icariine promotes the proliferation and differentiation of osteoblasts in vitro. The present study aimed to evaluate the effects of Icariine on lipopolysaccharide (LPS)-induced bone loss via an osteogenic-in vitro model and to elucidate the underlying molecular mechanisms. Here, we showed that Icariine restored LPS-induced bone loss in a dose-dependent manner without any cytotoxicity even at 100 µM in an osteogenic-in vitro model. Interestingly, Icariine restored the protein expression of Runx2, a key transcription factor for osteogenesis, but had no effect on its mRNA expression level. MiRNA-34c was dramatically upregulated after LPS stimulation; however, Icariine preincubation reversed miRNA-34c level. Western blot analysis showed that overexpression of miR-34c markedly inhibited the expression of osteogenic gene makers such as alkaline phosphatase (ALP), Runx2, OPN, and BMP2. ALP activity analysis and Alizarin Red S staining exhibited that both Icariine-induced osteogenic differentiation and mineral nodule formation were significantly inverted by overexpression of miR-34c. Western blot results also showed that Icariine notably inhibited LPS-induced phosphorylation of JNKs, p38, IkBα, IKKß, and p65. Taken together, our studies suggested that Icariine restored LPS-induced bone loss by downregulating miR-34c level and suppressing JNKs, p38, and NF-kB pathways, which highlighted the potential use of Icariine as a therapeutic agent in the treatment of bacteria-induced bone loss diseases.

The Clinical Effect of Acupuncture in the Treatment of Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Purpose. This study aims to determine the clinical efficacy of acupuncture therapy in the treatment of obstructive sleep apnea. Methods. A systematic literature search was conducted in five databases including PubMed, EMBASE, CENTRAL, Wanfang, and CNKI to identify randomized controlled trials (RCTs) on the effect of acupuncture therapy for obstructive sleep apnea. Meta-analysis was conducted using the RevMan version 5.3 software. Results. Six RCTs involving 362 subjects were included in our study. Compared with control groups, manual acupuncture (MA) was more effective in the improvement of apnea/hypopnea index (AHI), apnea index, hypopnea index, and mean SaO2. Electroacupuncture (EA) was better in improving the AHI and apnea index when compared with control treatment, but no statistically significant differences in hypopnea index and mean SaO2 were found. In the comparison of MA and nasal continuous positive airway pressure, the results favored MA in the improvement of AHI; there was no statistical difference in the improvement in mean SaO2. No adverse events associated with acupuncture therapy were documented. Conclusion. Compared to control groups, both MA and EA were more effective in improving AHI and mean SaO2. In addition, MA could further improve apnea index and hypopnea index compared to control.

[Acupuncture Therapy versus Disease-modifying Antirheumatic Drugs for the Treatment of Ankylosing Spondylitis--a Meta-analysis]. / Akupunktur versus krankheitsmodifizierende Antirheumatika in der Behandlung der ankylosierenden Spondylitis--eine Metaanalyse.

BACKGROUND: We conducted a meta-analysis evaluating the efficacy and safety of acupuncture compared to disease-modifying antirheumatic drugs in patients with ankylosing spondylitis. METHODS: Four databases including Pubmed, EMBASE, Cochrane library, and ISI Web of Science were searched in December 2014, taking also the reference section into account. Randomized controlled trials that aimed to assess the efficacy of acupuncture therapy were identified. The inclusion criteria for the outcome measurements were the clinical effect, ESR, occipital wall test, chest expansion, CRP and finger ground distance. Finally, six studies met these inclusion criteria. Two reviewers screened each article independently and were blinded to the findings of each other. RESULTS: We analyzed data from 6 RCTs involving 541 participants. Acupuncture therapy could further improve the clinical effect (OR = 3.01; 95% CI, 1.48-6.13; P = 0.002) and reduce ESR level (SMD = -0.77; 95% CI, -1.46 to -0.08; P = 0.03) compared to DMARDs; a combination of acupuncture and DMARDs could further improve clinical effect (OR = 3.20, 95% CI, 1.36-7.54; P = 0.008), occipital-wall distance (SMD = -0.84; 95% CI, -1.37 to -0.31; P = 0.002), chest expansion (SMD = 0.38; 95% CI, 0.16-0.60; P = 0.0009), and finger-ground distance (SMD = -0.48; 95% CI, -0.87 to -0.09; P = 0.02) as compared to DMARDs treatment alone. CONCLUSIONS: Our findings support that acupuncture therapy could be an option to relieve symptoms associated with AS. These results should be interpreted cautiously due to the generally poor methodological qualities of the included trials.

[Advancement in drug therapy of spinal cord injury].

With the increasing progress to know spinal cord injury (SCI) in experimental and clinical study and the confirming clinical effect to treat SCI with early methylprednisolone in ninety decade of 20th century, the mechanism of methylprednisolone therapy is understood continuously. Based on them above, a lot of new drugs are found effective for SCI. We want to give a review about it.

Effect of epimedium-derived phytoestrogen on bone turnover and bone microarchitecture in OVX-induced osteoporotic rats.

To investigate the preventive effect of epimedium-derived phytoestrogen (PE) on osteoporosis induced by ovariectomy (OVX) in rats, 11-month-old female Wistar rats were randomly divided into Sham, OVX and PE groups. One week after OVX, daily oral administration of PE (0.4 g.kg(-1).day(-1)) started in PE group, and rats in Sham and OVX groups were given vehicle accordingly. The administrations lasted for 12 weeks. The biological markers including serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) for bone turnover were evaluated at the end of the 12th week. On the 13th week, all the rats were sacrificed. The right proximal tibiae were removed, subjected to micro CT for determination of trabecular bone structure and then bone histomorphometry was performed to assess bone remodeling. The OVX rats were in a high bone turnover status as evidenced by increased bone formation markers and bone resorption markers. Treatment with PE could suppress the high bone turnover rate in OVX rats. Micro CT data revealed that PE treatment could ameliorate the deterioration of the micro-architecture of proximal tibiae induced by OVX, as demonstrated by greater bone volume, increased trabecular thickness and less trabecular separation in PE group in comparison with OVX group. The static and dynamic parameters of bone histomorphometry indicated that there were significant increases in bone formation variables and significant decreases in bone resorption variables between PE and OVX groups. The findings suggest that PE has a beneficial effect on trabecular bone in OVX rat model and this effect is possibly associated with stimulation of bone formation as well as inhibition of bone resorption.

Effects of Icariin on expression of OPN mRNA and type I collagen in rat osteoblasts in vitro.

To study the effects of Icariin on expression of osteopontin (OPN) mRNA and type I collagen in rat osteoblasts in vitro and to explore its possible mechanisms in preventing osteoporosis. OB was isolated from calvaria of new-born new-born fetal Sprague-Dawley (SD) rats by means of modified sequential collagenase digestion and incubated in MEM medium and the cell morphology was observed under inverted phase contrast microscope, OB was identified by alkaline phosphatase (ALP) staining. Different concentration (0.1 microg/mL, 1.0 microg/ml, 10 microg/mL) of Icariin was added to the OB and incubated. The effect of Icariin on the proliferation and osteogenesis of OB was monitored by MTT analysis. The expression of type I collagen was estimated with immunohistochemistry techniques. The expression levels of mRNA of OPN in the cells in every group were examined by reverse-transcriptase ploymerase chain reaction (RT-PCR). The expression of OPN mRNA and type I collagen was strengthened gradually with the increase of Icariin concentration and peaked with 10 microg/mL Icariin on the 5th day. Icariin could significantly promote the expression of OPN mRNA and type I collagen in rat osteoblasts in vitro. The levels of expression of OPN mRNA and type I collagen were changed with different concentration of Icariin. Icariin could effectively prevent and treat osteoporosis and promote the bone formation.