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Introduction: Manipulation under anesthesia (MUA) is often used for frozen shoulder treatment, but controversy still exists regarding MUA compared with conservative treatment. This research was conducted to compare the outcome between MUA and celecoxib (CLX) in secondary frozen shoulder. Methods: Patients with secondary frozen shoulder were randomized into two groups, an MUA plus exercise (EX) group and a CLX plus EX group. Clinical outcomes were documented at baseline and at 1 day, 2, 4, and 12 weeks after intervention, including Constant–Murley Score (CMS) for function, Pain Rating Index (PRI) and Present Pain Intensity (PPI) for pain, passive range of motion (ROM) measurements including external rotation, internal rotation, forward flexion, and abduction. Primary outcome was CMS. Secondary outcomes were PRI, PPI, and passive ROM. Results: Sixty-seven patients out of 68 in the MUA group and 66 out of 68 in the CLX group finished the entire study period. There were no significant differences in basic properties of the two groups before intervention. As the primary outcome, CMS changes in the MUA group improved faster than the CLX group. Secondary outcomes, passive ROM, and pain PPI were faster and significant in the MUA group from 1 day after intervention compared with CLX (P < 0.05). At 12 weeks, a statistically significant difference was not observed in the PPI (P > 0.05). A statistically significant difference was not observed in the PRI between groups in 1 day (P > 0.05). For the primary outcome, from 0 to 12 weeks the mean changes in CMS were 44.00 for MUA plus EX (95% CI 43.07–44.93, P < 0.001) and 27.09 for CLX plus EX (26.20–27.98, P < 0.001). The significant difference in improvement appeared from 2 weeks. Conclusion: To treat secondary frozen shoulder with MUA, this treatment could achieve better therapeutic effects on improvement of function, pain, and passive ROM than CLX did. Clinical Trial Registration: The trial was registered at www.chictr.org.cn, identifier ChiCTR2200060269. [ABSTRACT FROM AUTHOR]

Introduction: Patients with knee osteoarthritis (KOA) often complain about clinical symptoms affected by weather-related factors. The purpose of the present study was to use cross-sectional analysis to determine whether weather sensitivity was associated with clinical symptoms, as well as structure abnormalities, in KOA patients. Methods: Data from 80 participants were obtained from the Feng Hans Shi Effects on OA (FHS) study, an OA cohort study initiated in China in 2015. The weather sensitivity of each participant was determined by a self-reported questionnaire. The following measurements were used to assess clinical outcomes: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for symptoms, and semi-quantitative Whole-Organ Magnetic Resonance Imaging Score (WORMS) for cartilage defects and marrow abnormalities of magnetic resonance imaging (MRI). Chi-square with Cochran–Armitage test for trend and regression analysis were used to evaluate the associations between weather sensitivity and WOMAC and WORMS of KOA patients. Results: Most of the KOA participants (57.5%) perceived the weather as affecting their knee-joint clinical symptoms. After adjusting for age, gender, and body mass index (BMI), weather sensitivity was not only associated with knee pain [OR = 3.3 (95% CI 1.1, 9.9), P = 0.032], dysfunction [OR = 5.5 (95% CI 1.8, 16.8), P = 0.003], and overall clinical symptoms [OR = 3.3 (95% CI 1.1, 10.2), P = 0.034], but also associated with cartilage defect [OR = 3.1 (95% CI 1.1, 8.5), P = 0.027] and marrow abnormality [OR = 3.0 (95% CI 1.1, 8.1), P = 0.029]. Conclusions: In KOA patients, weather sensitivity was associated with clinical symptoms and structural abnormalities. Future longitudinal study is warranted for the causal relationship. Infographic: [ABSTRACT FROM AUTHOR]

Background/Aims: Bone marrow-derived mesenchymal stem cells (MSCs) are responsible for new bone formation during adulthood. Accumulating evidences showed that Osthole promotes the osteogenic differentiation in primary osteoblasts. The aim of this study was to investigate whether Osthole exhibits a potential to stimulate the osteogenic differentiation of MSCs and the underlying mechanism. Methods: MSCs were treated with a gradient concentration of Osthole (6.25 μM, 12.5 μM, and 25 μM). Cell proliferation was assessed by western blotting with the proliferating cell nuclear antigen (PCNA) and Cyclin D1 antibodies, fluorescence activated cell sorting (FACS), and cell counting kit 8 (CCK8). MSCs were cultured in osteogenesis-induced medium for one or two weeks. The osteogenic differentiation of MSCs was estimated by Alkaline Phosphatase (ALP) staining, Alizarin red staining, Calcium influx, and quantitative PCR (qPCR). The underlying mechanism of Osthole-induced osteogenesis was further evaluated by western blotting with antibodies in Wnt/β-catenin, PI3K/Akt, BMPs/ smad1/5/8, and MAPK signaling pathways. Results: Osthole inhibited proliferation of rat MSCs in a dose-dependent manner. Osthole suppressed osteogenic differentiation of rat MSCs by down-regulating the activities of Wnt/β-catenin and Erk1/2-MAPK signaling. Conclusions: Osthole inhibits the proliferation and osteogenic differentiation of rat MSCs, which might be mediated through blocking the Wnt/β-catenin and Erk1/2-MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

Background: Although patients with an anterior cruciate ligament (ACL) injury have a high risk of developing posttraumatic osteoarthritis (PTOA), the role of meniscus hypertrophy and mineralization in PTOA after an ACL injury remains unknown. Purpose/Hypothesis: The purpose of this study was to determine if menisci respond to abnormal loading and if an ACL injury results in meniscus hypertrophy and calcification. The hypotheses were that (1) abnormal mechanical loading after an ACL injury induces meniscus hypertrophy and mineralization, which correlates to articular cartilage damage in vivo, and (2) abnormal mechanical loading on bovine meniscus explants induces the overexpression of hypertrophic and mineralization markers in vitro. Study Design: Controlled laboratory study. Methods: In vivo guinea pig study (hypothesis 1): Three-month-old male Hartley guinea pigs (n = 9) underwent ACL transection (ACLT) on the right knee; the left knee served as the control. Calcification in the menisci was evaluated by calcein labeling 1 and 5 days before knee harvesting at 5.5 months. Cartilage and meniscus damage and mineralization were quantified by the Osteoarthritis Research Society International score and meniscus grade, respectively. Indian hedgehog (Ihh), matrix metalloproteinase–13 (MMP-13), collagen type X (Col X), progressive ankylosis homolog (ANKH), ectonucleotide pyrophosphatase/phosphodiesterase–1 (ENPP1), alkaline phosphatase (ALP), inorganic pyrophosphate (PPi), and inorganic phosphate (Pi) concentrations were evaluated by immunohistochemistry and enzyme-linked immunosorbent assay. In vitro bovine meniscus explant study (hypothesis 2): Bovine meniscus explants were subjected to 25% strain at 0.3 Hz for 1, 2, and 3 hours. Cell viability was determined using live/dead staining. The levels of mRNA expression and protein levels were measured using real-time quantitative reverse transcription polymerase chain reaction and Western blot after 24, 48, and 72 hours in culture. The conditioned medium was collected for sulfated glycosaminoglycan (GAG) release and Pi/PPi assay. Results: In vivo guinea pig study: Meniscus size and area as well as intensity of meniscus calcification were significantly increased in the ACLT group compared with the control group. Both calcified area and intensity were correlated with cartilage damage in the ACLT group (meniscus calcified area: r = 0.925, P < .0001; meniscus calcified intensity: r = 0.944, P < .0001). Ihh, MMP-13, Col X, ANKH, ENPP1, and ALP expression were increased in the ACLT group compared with the control group. The Pi level and Pi/PPi ratio increased by 63% and 42%, respectively, in the ACLT group compared with the control group. In vitro bovine meniscus explant study: Cell death was found in the superficial zone of the bovine meniscus explants after loading for 3 hours. The mRNA expression and protein levels of MMP-13, ANKH, ENPP1, and ALP were up-regulated in all 3-hour loaded samples. The Pi/PPi ratio and sulfated GAG content in the culture medium were increased in the 3-hour loaded group. Conclusion: Meniscus hypertrophy and mineralization correlated to cartilage degeneration after ACL injuries. Clinical Relevance: The study data suggest that the suppression of meniscus hypertrophy and calcification may decrease the risk of PTOA after ACL injuries. [ABSTRACT FROM AUTHOR]

Background/Aims: Cartilage destruction is thought to be the major mediator of osteoarthritis. Recent studies suggest that inhibition of subchrondral bone loss by anti-osteoporosis (OP) drug can protect cartilige erosion. Osthole, as a promising agent for treating osteoporosis, may show potential in treating osteoarthritis. The purpose of this study was to investigate whether Osthole affects the proliferation and catabolism of rat chondrocytes, and the degeneration of cartilage explants. Methods: Rat chondrocytes were treated with Osthole (0 μM, 6.25 μM, 12.5 μM, and 25 μM) with or without IL1-ß (10ng/ml) for 24 hours. The expression levels of type II collagen and MMP13 were detected by western Blot. Marker genes for chondrocytes (A-can and Sox9), matrix metalloproteinases (MMPS), aggrecanases (ADAMTS5) and genes implicated in extracellular matrix catabolism were evaluated by qPCR. Cell proliferation was assessed by measuring proliferating cell nuclear antigen (PCNA) expression and fluorescence activated cell sorter. Wnt7b/ß-catenin signaling was also investigated. Cartilage explants from twoweek old SD rats were cultured with IL-1ß, Osthole and Osthole plus IL-1ß for four days and glycosaminoglycan (GAG) synthesis was assessed with toluidine blue staining and Safranine O/Fast Green FCF staining, collagen type II expression was detected by immunofluorescence. Results: Osthole reduced expression of chondrocyte markers and increased expression of MMP13, ADAMTS5 and MMP9 in a dose-dependent manner. Catabolic gene expression levels were further improved by Osthole plus IL-1ß. Osthole inhibited chondrocyte proliferation. GAG synthesis and type II collagen were decreased in both the IL-1ß groups and the Osthole groups, and significantly reduced by Osthole plus IL-1ß. Conclusions: Our data suggested that Osthole increases the catabolism of rat chondrocytes and cartilage explants, this effect might be mediated through inhibiting Wnt7b/ß-catenin pathway. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this study was to investigate how Osthole affects glioma cell proliferation, apoptosis, invasion and migration. Methods: Rat glioma cells were treated with different concentrations of Osthole (0 µM, 25 µM, 50 µM, and 100 µM). Cell proliferation was assessed by measuring PCNA expression and CCK8 assay at different time points. Apoptosis was evaluated by measuring the expression of pro-apoptotic protein including Bax, Bcl2, PARP, and cleaved Caspase3, and of anti-apoptotic protein Survivin. Cell migration and invasion were assessed using different methods. Signaling pathways such as PI3K/Akt and MAPK, which are involved in the development of glioma cells, were also investigated in this study. Results: Treatment with Osthole markedly inhibits glioma cell proliferation, as assessed by western blot with the PCNA antibody. Osthole also induces cell apoptosis by upregulating the expression of pro-apoptotic proteins, and by reducing the expression of anti-apoptotic factors. Moreover, C6 cell migration and invasion were efficiently inhibited in groups treated with Osthole, compared to the control group. Additionally, inhibition of PI3K/Akt and MAPK signaling pathway was also observed in C6 cells treated with Osthole. Conclusions: Our findings showed an anti-cancer effect of Osthole on glioma cells, including the proliferation inhibition, apoptosis induction, and migration/invasion inhibition. Further investigation in C6 glioma cells implicated the role of Osthole in essential pathways controlling glioma cell progression. Taken together, our data suggested that Osthole may have a potential application in glioma therapy. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Many Sox proteins play important roles both in mesoderm and ectoderm development. It is reported that Sox2, a member of this family, is essential for the maintenance of the self-renewal of embryonic stem cells (ES) and neural stem cells (NSCs). To investigate whether Sox2 participates in mesoderm development besides ectoderm, Sox2 was introduced into C3H10T1/2 cells. Methods: We produced recombinant retrovirus expressing Sox2 in GP2-293t cells and infected the virus into C3H10T1/2 cells. Growth property, alkaline phosphatase (ALP) staining, mineralized nodules, osteogenic gene expression and related signal pathways were analysed and compared between Sox2-expressing cells and control cells. Results: Sox2 over-expression led to increased proliferation of C3H10T1/2 cells, activation of Wnt/β-catenin and p38MAPK pathways. When cultured in osteogenic differentiation medium, ALP and mineralized nodules formation were inhibited in Sox2 over-expressing cells with down-regulation of osteogenic gene expression as well as inhibition of Wnt/β-catenin and p38MAPK pathways. Conclusions: All these data suggested that over-expression of Sox2 promoted proliferation and inhibited osteoblast differentiation of C3H10T1/2 cells. [ABSTRACT FROM AUTHOR]