[Show abstract][Hide abstract] ABSTRACT: The anticancer effect of Scutellaria baicalensis extract has recently become a topic of interest. In this study, the anticancer effects and underlying mechanisms of wogonoside, the main constituent of Scutellaria baicalensis, were investigated in a human hepatocellular carcinoma (HCC) cell line in vitro. The effects of wogonoside on the proliferation, cell cycle progression and apoptosis of hepatocellular carcinoma cells were examined. Western blotting was employed to analyze the proteins associated with the biological effects of wogonoside. Wogonoside exerted anti‑proliferation properties in vitro. HCC cell growth was attenuated by wogonoside (8 μM) treatment. Cell cycle progression analysis and DNA ladder assay revealed that apoptosis was enhanced in wogonoside‑treated cells and that cell cycle arrest occurred in the G2/M phase. It was also demonstrated that increased apoptosis was accompanied by increased levels of Bax protein and decreased levels of Bcl‑2 protein. The results of this study suggest that wogonoside may represent a potential therapeutic agent against HCC.
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to investigate the in vitro effect of osteopontin (OPN) on the expression of hypoxia-inducible factor-2α (HIF-2α) in chondrocytes and the role of OPN in osteoarthritis (OA). Cartilage was purified from the tibial surfaces of patients with OA of the knee and cultured in vitro to obtain chondrocytes. Recombinant human OPN (rhOPN) and OPN small interfering RNA (siRNA) were used to treat the chondrocytes, and the changes in the expression levels of the HIF-2α gene were measured. An anti-CD44 blocking monoclonal antibody (mAb) was used to determine the probable ligand-receptor interactions. Reverse transcription-quantitative polymerase chain reaction assays were designed and validated with SYBR® Green dyes for the simultaneous quantiﬁcation of the mRNA expression levels of OPN and HIF-2α. The mRNA expression level of HIF-2α was markedly decreased in the rhOPN-treated group compared with that in the control group; by contrast, OPN siRNA increased HIF-2α gene expression. CD44 blocking mAb suppressed the inhibitory effect of OPN on HIF-2α mRNA expression. The results of the present study suggest that OPN may play a protective role in OA by inhibiting HIF-2α gene expression in osteoarthritic chondrocytes through CD44 interaction.
Experimental and therapeutic medicine 06/2015; 9(6):2415-2419. DOI:10.3892/etm.2015.2434 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies have demonstrated that osteopontin (OPN) levels are elevated in the synovial fluid and articular cartilage, and are associated with the severity of knee osteoarthritis (OA). However, the role of OPN in the pathogenesis of OA has yet to be elucidated. The present study aimed to investigate the effects of OPN on the expression of the aggrecanases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and ADAMTS5, in human OA chondrocytes, as they serve a key function in aggrecan degradation. Human OA chondrocytes were obtained from the knees of 16 patients with OA, and subsequently cultured in a monolayer. The chondrocytes were divided into three groups, which included the control (no treatment), N-OPN (treated with 100 ng/ml OPN, the normal circulating OPN concentration) and the H-OPN groups (treated with 1 µg/ml OPN, a high OPN concentration). Reverse transcription-quantitative polymerase chain reaction was performed to quantify the relative mRNA expression levels of ADAMTS4, ADAMTS5 and aggrecan in the chondrocytes. The mRNA expression levels of ADAMTS4 were significantly reduced in the N-OPN and H-OPN groups when compared with the control group (P<0.0001). In addition, the mRNA expression levels of ADAMTS4 were lower in the H-OPN group when compared with the N-OPN group (P<0.001). However, no statistically significant difference was observed in the relative mRNA expression levels of ADAMTS5 among the three groups (P>0.05). Furthermore, the mRNA expression levels of aggrecan were higher in the N-OPN and H-OPN groups when compared with the control group (P<0.0001), and a statistically significant difference was observed between the N-OPN and H-OPN groups with regard to the mRNA expression of aggrecan (P<0.0001). These results demonstrated that OPN may exert a protective effect in human OA chondrocytes against aggrecan degradation by suppressing the expression of ADAMTS4.
Experimental and therapeutic medicine 05/2015; 9(5):1979-1983. DOI:10.3892/etm.2015.2310 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoarthritis (OA) is a degenerative disease, which is characterized by articular cartilage destruction, and mainly affects the older people. The extracellular matrix (ECM) provides a vital cellular environment, and interactions between the cell and ECM are important in regulating many biological processes, including cell growth, differentiation, and survival. However, the pathogenesis of this disease is not fully elucidated, and it cannot be cured totally. Integrins are one of the major receptors in chondrocytes. A number of studies confirmed that the chondrocytes express several integrins including α5β1, αVβ3, αVβ5, α6β1, α1β1, α2β1, α10β1, and α3β1, and some integrins ligands might act as the OA progression biomarkers. This review focuses on the functional role of integrins and their extracellular ligands in OA progression, especially OA cartilage. Clear understanding of the role of integrins and their ligands in OA cartilage may have impact on future development of successful therapeutic approaches to OA.
Rheumatology International 09/2014; 35(5). DOI:10.1007/s00296-014-3137-5 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Wnt signaling pathway regulates some of the crucial aspects of cellular processes. The beta-catenin dependent Wnt signaling (Wnt/β-catenin) pathway controls the expression of key developmental genes, and acts as an intracellular signal transducer. The association of Wnt/β-catenin pathway is often reported with different cancers. In this study, we have reviewed the association of Wnt/β-catenin pathway with bone cancers, focusing on carcinogenesis and therapeutic aspects. Wnt/β-catenin pathway is a highly complex and unique signaling pathway, which has ability to regulate gene expression, cell invasion, migration, proliferation, and differentiation for the initiation and progression of bone cancers, especially osteosarcoma. Association of Wnt/β-catenin pathway with chondrosarcoma, Ewing's sarcoma and chondroma is also documented. Recently, targeting Wnt/β-catenin pathway has gained significant interests as a potential therapeutic application for the treatment of bone cancers. Small RNA technology to knockdown aberrant Wnt/β-catenin or inhibition of β-catenin expression by natural component has shown promising effects against bone cancers. Advances in understanding the mechanisms of Wnt signaling and new technologies have facilitated the discovery of agents that can target and regulate Wnt/β-catenin signaling pathway, and these may provide a basement for the innovative therapeutic approaches in the treatment of bone cancers.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: The purpose of this quantitative meta-analysis is to appraise the efficacy and side effects of intra-articular morphine in patients undergoing arthroscopic knee surgery. METHODS: The comprehensive literature search, using Medline (1966 to 2013), the Cochrane Central Register of Controlled Trials, and EMBASE databases, was conducted to identify randomized placebo-controlled trials that used single-dose intra-articular morphine for postoperative pain. The relative risk (RR), standardized mean difference (SMD), and their corresponding 95% confidence intervals (CIs) were calculated using statistical software. RESULTS: Twenty-six articles were included in the meta-analysis. The acute postoperative visual analog scale (VAS) pain scores of the morphine group compared with the control group were significantly lower (SMD, -1.16; 95% CI, -1.79 to -0.53; P = .0003). The number of patients requiring supplementary analgesia was also significantly reduced (RR, 0.80; 95% CI, 0.70 to 0.93; P = .008), and there was a significant difference in the time to first analgesic request (SMD, 1.47; 95% CI, 0.49 to 2.44; P = .003) when the morphine group was compared with the placebo group. However, there was no significant difference in side effects between the morphine group and the control group (RR, 0.93; 95% CI, 0.67 to 1.28; P = .65). CONCLUSIONS: The key findings of the present study were that the administration of single-dose intra-articular morphine at the end of arthroscopic knee surgery provided better pain relief, reduced the need for supplementary analgesics, and lengthened the time interval before the first request for additional analgesic medication, all with short-term side effects similar to those of the saline placebo. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I-II studies.
Arthroscopy The Journal of Arthroscopic and Related Surgery 06/2013; 29(8). DOI:10.1016/j.arthro.2013.04.005 · 3.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimThe purposes of this study were to investigate senescence-associated beta-galactosidase (SA-beta-Gal) levels in articular cartilage of knee osteoarthritis (OA) and the relationship with severity of the disease. Methods
All the 50 cartilage tissues, including normal (controls) and OA cartilage were ascribed to four groups of normal, mild lesions, moderate lesions and severe lesions on the basis of the modified Mankin score. Immunohistochemistry was used to assess the SA-beta-Gal expression in articular cartilage. ResultsNo SA-beta-Gal staining was observed in the normal articular cartilage samples. SA-beta-Gal staining was found in a subset of the chondrocytes close to the lesion site of mild, moderate and severe damaged knee OA cartilage. The percentage of SA-beta-Gal-positive chondrocytes in articular cartilage was 0% in controls, 13.00 ± 5.77% in mild lesions, 31.65 ± 6.91% in moderate lesions and 51.95 ± 6.21% in severe lesions. SA-beta-Gal expression in mild lesions, moderate lesions and severe lesions was higher compared with that of controls (P < 0.0001). SA-beta-Gal expression in moderate lesions and severe lesions were higher with respect to mild lesion samples (P < 0.0001). SA-beta-Gal expression in severe lesions was elevated compared with those of moderate lesions (P < 0.0001). Subsequent analysis showed that articular cartilage SA-beta-Gal levels correlated with severity of disease (Spearman's ρ = 0.94, P < 0.0001). ConclusionSA-beta-Gal expression in articular cartilage is associated with progressive knee OA joint damage and is a potential indictor of disease severity.
International Journal of Rheumatic Diseases 05/2013; DOI:10.1111/1756-185X.12096 · 1.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The white-white tears (meniscus lesion completely in the avascular zone) are without blood supply and theoretically cannot heal. Basal research has demonstrated that menisci are unquestionably important in load bearing, load redistribution, shock absorption, joint lubrication and the stabilization of the knee joint. It has been proven that partial or all-meniscusectomy results in an accelerated degeneration of cartilage and an increased rate of early osteoarthritis. Knee surgeons must face the difficult decision of removing or, if possible, retaining the meniscus; if it is possible to retain the meniscus, surgeons must address the difficulties of meniscal healing. Some preliminary approaches have progressed to improve meniscal healing. However, the problem of promoting meniscal healing in the avascular area has not yet been resolved. The demanding nature of the approach as well as its low utility and efficacy has impeded the progress of these enhancement techniques. Platelet-rich plasma (PRP) is a platelet concentration derived from autologous blood. In recent years, PRP has been used widely in preclinical and clinical applications for bone regeneration and wound healing. Therefore, we hypothesize that the application of platelet-rich plasma for white-white meniscal tears will be a simple and novel technique of high utility in knee surgery.
Medical science monitor: international medical journal of experimental and clinical research 08/2012; 18(8):HY47-50. DOI:10.12659/MSM.883254 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF). However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke.
Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC), bone mineral density (BMD), bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined.
Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption), affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface), and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover.
The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption.
[Show abstract][Hide abstract] ABSTRACT: Based on a rat model of human relatively high exposure to cigarette smoke, this study aimed to estimate whether Epimedium pubescen flavonoid (EPF) may prevent a smoke-induced decrease in bone mineral density (BMD) and weakening of the biomechanical properties of bone.
Fifty male Wistar rats were randomized into five groups: controls, passively smoking groups and passively smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive cigarette smoking was prepared by breeding male rats in a cigarette-smoking box for 4 months. Bone metabolic makers, BMD and biomechanical properties of the femoral distal end and femoral diaphysis were examined.
Exposure to cigarette smoke decreased the BMD, affected bone turnover (inhibited bone formation and stimulated its resorption) and weakened the biomechanical properties of the femur at its distal end and diaphysis. EPF supplementation during cigarette smoke exposure prevented the decrease in BMD, accelerated bone turnover and weakened the biomechanical properties of bone.
Our data suggest that EPF supplementation can prevent the adverse effects of smoke exposure on BMD and biomechanical properties by inhibiting bone turnover and preventing bone resorption, and in this way it can decrease the risk of bone fractures.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the effect of hyaluronic acid (HA) on the expression of osteopontin (OPN) and CD44 mRNA of fibroblast-like synoviocytes (FLS) in the patients with osteoarthritis (OA) of the knee. FLS were obtained from the knees of 10 patients with OA. Real-time quantitative polymerase chain reaction (Q-PCR) was used to assess the expression of the OPN mRNA and CD44 mRNA. The relative OPN mRNA expression in HA group (6.47 ± 2.30-fold) was significantly higher than in the control group (P = 0.045, P < 0.05), while in HYL group (0.65 ± 0.21-fold) it was lower than in the control group (P = 0.037, P < 0.05), and the difference in OPN mRNA expression between HA group and HYL group also showed statistically significant (P = 0.001, P < 0.05); however, there was no significant difference between each group of the relative CD44 mRNA expression (P > 0.05). Our study showed that HA can upregulate OPN mRNA expression in OA fibroblast-like synoviocytes, and the high expression of OPN mRNA in OA may be a result of increased HA level of OA synovitis; however, HA cannot affect the CD44 mRNA expression in OA fibroblast-like synoviocytes, and the high expression of CD44 mRNA in OA may be not a result of increased HA level of OA synovitis.
Rheumatology International 01/2012; 33(1). DOI:10.1007/s00296-011-2339-3 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many studies have identified smoking as a risk factor for osteoporosis, but it is unclear whether passive smoking has an effect on bone mineral density and bone turnover and if such an effect could cause osteoporosis.The purpose of the study was to investigate the effect of passive smoking on bone mineral density (BMD) and bone turnover and the relationship between BMD and bone turnover in female rat.
Forty-eight female Wistar rats were randomized into six groups: 2-month, 3-month,4-month smoke-exposed rats and their controls. A rat model of passive cigarette smoking was prepared by breeding female rats in a cigarette-smoking box for 2, 3 or 4 months. Serums were analyzed for levels of osteocalcin, bone-specific alkaline phosphatase (b-ALP) and Tartrate-resistant acid phosphatase 5b (TRACP 5b). BMD was assessed at lumbar vertebrae and femur by dual energy X-ray absorptiometry in passive smoking rats and in control rats.
BMD of lumbar spine and femur was lower in 4-month smoke-exposed female rats than that in controls. However, there was no significant difference in serum osteocalcin levels between smoke-exposed rats and controls. Significantly lower b-ALP and higher TRACP 5b were found in the 3-month or 4-month smoke-exposed rats compared to controls. Subsequent analysis showed that b-ALP positively correlated with BMD of the lumbar vertebrae(r = 0.764, P = 0.027) and femur(r = 0.899, P = 0.002) in 4-month smoke-exposed female rats. Furthermore, TRACP 5b levels negatively correlated with BMD of lumbar vertebrae (r = -0.871, P = 0.005) and femur (r = -0.715, P = 0.046) in 4-month smoke-exposed female rats.
Our data suggest that smoke exposure can inhibit bone formation and increase bone resorption. The hazardous effects of passive smoking on bone status are associated with increased bone turnover in female rat.