Safety and Effectiveness of Orthopaedic Medical Staff in Providing Support in Combating the COVID-19 Pandemic: A Retrospective Investigation from Wuhan, China.

OBJECTIVE: To evaluate whether it is safe and effective for orthopaedic medical staff to provide support to the work against COVID-19. METHODS: One hundred and twenty-two orthopaedic medical staff from the orthopaedic center of Zhongnan Hospital of Wuhan University were included in this retrospective investigation. A total of 43 surgeons and 69 nurses provided medical support in the treatment of COVID-19 patients from 1 January 2020 to 8 April 2020 in four different hospitals in Wuhan. We collected data on the age, gender, and body temperature of orthopaedic medical staff, as well as the results for their chest CT scans, SARS-CoV-2 RNA, SARS-CoV-2 IgM and SARS-CoV-2 IgG tests, and training and examinations on COVID-19 knowledge. We also collected data on the time span of work, the number of infected staff during the support period, the number of COVID-19 patients the surgeons treated and the cure rate, the performance of the surgeons as assessed by the specialists and patients, and the number of infected staff during the pandemic. RESULTS: Among the 49 surgeons and 73 nurses, 43 surgeons and 69 nurses provided support against COVID-19. A total of 12 surgeons and 11 nurses provided support in the fields of respiration, intensive care, and emergency. A total of 34 surgeons and 58 nurses worked in the designated wards restructured for COVID-19 in the orthopaedic building. The average time span of work for the surgeons and nurses was 14.78 ± 3.64 days and 24.77 ± 7.58 days, respectively. No staff were infected during the support period. Over 1000 patients were received in the fever clinic by orthopaedic surgeons. The overall number of the treated hospitalized patients was 622. Among these patients, 226 cases were mild, 318 were mild to moderate, and 58 were severe or critical. The cure rate was 96.01%, 99.37%, and 52.00% respectively. The performance of the surgeons was scored 87.02 ± 3.17 and 90.69 ± 3.58 by the specialists and the patients, respectively. During the whole pandemic, 3 surgeons and 3 nurses who did not participate in the support work were infected in the early stages. The morbidity of all the orthopaedic staff was 4.92% during the whole pandemic, while no one was infected during the support work. CONCLUSION: Our investigation indicated that although they worked outside their specialty, it was safe and effective for the orthopaedic staff to provide medical support in the work against COVID-19 with adequate precautions and proper training.

Ryanodine receptor 1 mediated dexamethasone-induced chondrodysplasia in fetal rats.

BACKGROUND: Osteoarthritis is caused by cartilage dysplasia and has fetal origin. Prenatal dexamethasone exposure (PDE) induced chondrodysplasia in fetal rats by inhibiting transforming growth factor ß (TGFß) signaling. This study aimed to determine the effect of dexamethasone on fetal cartilage development and illustrate the underlying molecular mechanism. METHODS: Dexamethasone (0.2 mg/kg.d) was injected subcutaneously every morning in pregnant rats from gestational day (GD) 9 to GD21. Harvested fetal femurs and tibias at GD21 for immunofluorescence and gene expression analysis. Fetal chondrocytes were treated with dexamethasone (100, 250 and 500 nM), endoplasmic reticulum stress (ERS) inhibitor, and ryanodine receptor 1 (RYR1) antagonist for subsequent analyses. RESULTS: In vivo, prenatal dexamethasone exposure (PDE) decreased the total length of the fetal cartilage, the proportion of the proliferation area and the cell density and matrix content in fetal articular cartilage. Moreover, PDE increased RYR1 expression and intracellular calcium levels and elevated the expression of ERS-related genes, while downregulated the TGFß signaling pathway and extracellular matrix (ECM) synthesis in fetal chondrocytes. In vitro, we verified dexamethasone significantly decreased ECM synthesis through activating RYR 1 mediated-ERS. CONCLUSIONS: PDE inhibited TGFß signaling pathway and matrix synthesis through RYR1 / intracellular calcium mediated ERS, which ultimately led to fetal dysplasia. This study confirmed the molecular mechanism of ERS involved in the developmental toxicity of dexamethasone and suggested that RYR1 may be an early intervention target for fetal-derived adult osteoarthritis.

Dexamethasone causes calcium deposition and degeneration in human anterior cruciate ligament cells through endoplasmic reticulum stress.

BACKGROUND: Dexamethasone is widely used in the treatment of joint diseases due to its anti-inflammatory properties. However, it can cause serious adverse effects. The anterior cruciate ligament (ACL) is an important stabilizer of the knee joint. However, the effect of dexamethasone treatment on the ACL is unclear. OBJECTIVE: This study aims to explore the effects of dexamethasone on ACL tissues and cells through in vitro and in vivo experiments. RESULTS: In vitro, we found that after treatment with dexamethasone, human ACL cell apoptosis was increased, type I collagen (COL1A1) content was decreased, mineralization related genes (ENPP1 and ANKH) and calcified nodules were increased, and endoplasmic reticulum stress (ERS) was enhanced. However, ERS inhibitors could significantly inhibit the increase in calcification and the decrease in COL1A1 induced by dexamethasone. In vivo, Wistar rats received the infra-articular injection with dexamethasone (0.5 mg/kg) for 8 weeks. We found that dexamethasone treatment decreased the COL1A1 content and increased the COL2A1 content in the ACL tissues of rats and that chondroid differentiation and mineralization occurred. Meanwhile, the expression of ERS-related proteins was increased. CONCLUSION: Dexamethasone increased the calcification of ACL cells and caused ACL degeneration through ERS, suggesting that long-term treatment with dexamethasone may cause adverse effects on ACL tissue and increase the risk of long-term rupture.

Prenatal nicotine exposure increases osteoarthritis susceptibility in male elderly offspring rats via low-function programming of the TGFß signaling pathway.

Epidemiological investigations indicate that effects related to prenatal adverse environments on the organs of the offspring could continue to adulthood. This study intends to confirm that prenatal nicotine exposure (PNE) increases the susceptibility of osteoarthritis (OA) in the male offspring, and to explore the potential intrauterine programming mechanism. During pregnancy, rats were divided into a PNE group and a control group. After birth, rats were given a high-fat diet for 6 months and long-distance running for 6 weeks. The rats were euthanized at 18 months after birth (PM18) and on gestational day 20 (GD20), respectively. Knee joints were collected for histochemistry, immunohistochemistry, and quantitative polymerase chain reaction (qPCR) assays. Histological analyses and the Mankin's score showed increased cartilage destruction and accelerated OA progression in adult offspring from the PNE group. Immunohistochemistry results showed decreased expression of transforming growth factor beta (TGFß) signaling pathway. Furthermore, the expression of apoptosis factors (caspase-3 and caspase-8), inflammatory factors [interleukin (IL)-1, IL-6] and matrix degradation enzymes [matrix metalloproteinase (MMP)-3, MMP-13] were also significantly increased. Traced back to the intrauterine period, it was found that the number of chondrocytes and the contents of Col2A1 and aggrecan in the matrix in the PNE group were decreased. And, the expression of the TGFß signaling pathway was inhibited. These results suggested that PNE enhanced the susceptibility of OA in male elderly offspring rats by down-regulating TGFß signaling, which increased articular cartilage local inflammation, matrix degradation, and cell apoptosis. This study confirmed the developmental origin of OA, and clarified the congenital and the living environment impact on the occurrence and development of OA. Our findings provide a theoretical and experimental basis for OA early prevention.

Effects of Enhanced Recovery After Surgery in Total Knee Arthroplasty for Patients Older Than 65 Years.

OBJECTIVES: To explore the safety and efficacy of the enhanced recovery after surgery (ERAS) program for elderly total knee arthroplasty (TKA) patients. METHODS: A prospective controlled study was conducted for patients older than 65 years, who would undergo unilateral TKA with a minimum follow-up of 2 years. Patients were divided into an ERAS group (n = 106) and a traditional group (n = 141) based on the patients' willingness to participate in the ERAS program. Baseline parameters of American Society of Anesthesiologists classification and comorbidity were recorded. Complication, mortality, knee function assessment using knee society score and knee range of motion, and perioperative clinical outcomes were compared between the two groups. RESULTS: There were no significant differences between the two groups in terms of baseline parameters. Although no significant differences were found in postoperative nausea and vomiting, urinary tract infection, deep venous thrombosis, pulmonary embolism, wound delayed healing, superficial infection, and deep infection, there were significantly fewer total complications in the ERAS group (26/106 vs 52/141; P = 0.039). No significant difference was found in short-term mortality (1/106 vs 3/141; P = 0.836) between the two groups. There were no significant differences in preoperative visual analogue scale (VAS), knee society score (KSS), and range of motion (ROM) between the two groups. Lower VAS scores were found in the ERAS group at time of postoperative day (POD) 1 (P = 0.012) and POD 5 (P = 0.020); no significant differences were observed at time of postoperative month (POM) 1 and final follow-up. Higher KSS scores were found in the ERAS group at time of POD 1 (P = 0.013), and POD 5 (P = 0.011), no significant differences were observed at time of POM 1 and final follow-up. Increased ROM degree was found in the ERAS group at time of POD 1 (P = 0.021); no significant differences were observed at time of POD 5, POM 1 and final follow-up. Decreased intraoperative blood loss (P < 0.001), total blood loss (P < 0.001), transfusion rate (P = 0.004), and length of stay (P < 0.001) were found in the ERAS group; no significant differences were found in operative time and hospitalization costs between the two groups. CONCLUSION: The ERAS program is safer and more efficacious in elderly TKA patients compared to the traditional pathway. It could effectively relieve perioperative pain and improve joint function, and reduce blood transfusion, length of stay, and total complications without increasing short-term mortality.

Survival outcome among patients with Ewing's sarcoma of bones and joints: a population-based cohort study

ABSTRACT BACKGROUND: The aim here was to elucidate the current survival condition of patients diagnosed with Ewing's sarcoma of the bones and joints and determine independent risk factors associated with the prognosis. DESIGN AND SETTING: Retrospective cohort study based on the Surveillance, Epidemiology and End Results (SEER) database in the United States. METHODS: We identified 397 patients who were diagnosed with Ewing's sarcoma of the bones and joints between January 2004 and December 2013. The multivariate Cox proportional hazards model was used to determine factors associated with the risk of death by adjusting for various factors. RESULTS: The one, two and five-year disease-specific survival rates were 89.08%, 78.08% and 62.47%, respectively. The factors related to death were age (≥ 18 years versus < 18 years; hazard ratio, HR = 1.77; 95% confidence interval, CI: 1.38-2.31); tumor site (extremity versus spine and pelvis; HR = 2.03; 95% CI: 1.31-2.62); tumor size (> 10 cm versus ≤ 10 cm; HR = 1.78; 95% CI: 1.34-2.56); and type of treatment (surgery alone versus radiotherapy with surgery; HR = 0.51; 95% CI: 0.38-0.89; or radiotherapy alone versus radiotherapy with surgery; HR = 1.61; 95% CI: 1.10-2.39; or no treatment versus radiotherapy with surgery; HR = 1.86; 95% CI: 1.23, 2.58). CONCLUSIONS: Patients with Ewing's sarcoma showed poor survival in situations of age ≥ 18 years, tumor size > 10 cm, receiving radiotherapy alone and receiving no treatment. Patients undergoing surgery alone had better survival.

Research progress of epigenetic biomarkers in the early diagnosis and treatment of human diseases.

Abnormal epigenetic modifications are common in many diseases (such as tumors, senile and developmental diseases), and can influence the pathogenesis and progression of these diseases. Various studies demonstrated that abnormal epigenetic changes could be used as biomarkers for diagnosis of the disease status and prognosis of disease progression. The reversibility and controllability of epigenetic modifications also offer an opportunity to develop new strategies for the early prevention and treatment of diseases. In this review, we provide a brief overview of the latest discoveries in three areas of epigenetic research, i.e., DNA methylation, histone modifications and non-coding RNAs, and their potential applications in early diagnosis and treatment of tumors, senile and developmental diseases. We hope to provide some insights and references in developing strategies for the diagnosis and treatment of these diseases.

Survival outcome among patients with Ewing's sarcoma of bones and joints: a population-based cohort study.

BACKGROUND: The aim here was to elucidate the current survival condition of patients diagnosed with Ewing's sarcoma of the bones and joints and determine independent risk factors associated with the prognosis. DESIGN AND SETTING: Retrospective cohort study based on the Surveillance, Epidemiology and End Results (SEER) database in the United States. METHODS: We identified 397 patients who were diagnosed with Ewing's sarcoma of the bones and joints between January 2004 and December 2013. The multivariate Cox proportional hazards model was used to determine factors associated with the risk of death by adjusting for various factors. RESULTS: The one, two and five-year disease-specific survival rates were 89.08%, 78.08% and 62.47%, respectively. The factors related to death were age (≥ 18 years versus < 18 years; hazard ratio, HR = 1.77; 95% confidence interval, CI: 1.38-2.31); tumor site (extremity versus spine and pelvis; HR = 2.03; 95% CI: 1.31-2.62); tumor size (> 10 cm versus ≤ 10 cm; HR = 1.78; 95% CI: 1.34-2.56); and type of treatment (surgery alone versus radiotherapy with surgery; HR = 0.51; 95% CI: 0.38-0.89; or radiotherapy alone versus radiotherapy with surgery; HR = 1.61; 95% CI: 1.10-2.39; or no treatment versus radiotherapy with surgery; HR = 1.86; 95% CI: 1.23, 2.58). CONCLUSIONS: Patients with Ewing's sarcoma showed poor survival in situations of age ≥ 18 years, tumor size > 10 cm, receiving radiotherapy alone and receiving no treatment. Patients undergoing surgery alone had better survival.

An intergenerational effect of neuroendocrine metabolic programming alteration induced by prenatal ethanol exposure in rats.

Prenatal ethanol exposure (PEE) induces hypothalamic-pituitary-adrenal (HPA) axis-related neuroendocrine metabolic programming alteration in the first generation (F1) rats. In this study, the HPA hormones and glucose/lipid phenotypes under basal state and stressed condition induced by a fortnight ice-water swimming were examined in F2 to verify the intergenerational effect. Under the basal state, serum corticosterone (CORT) and glucose of some PEE groups were lowered while those of serum triglycerides (TG) were increased comparing with controls. Following chronic stress, the percentage increase in CORT from the basal state tended to be greater for some PEE groups compared with controls while the percentage reduction of glucose and percentage elevation of TG were smaller. These results revealed that the low basal activity and hyper-responsiveness of the HPA axis as well as glucocorticoid-associated glucose and lipid phenotypic alterations were partially retained in F2, which indicates PEE-induced neuroendocrine metabolic programming alteration may have an intergenerational effect.

Thermal Preconditioning May Prevent Tendon Adhesion by Up-Regulating HSP72 in Rats.

BACKGROUND/AIMS: The study aims to determine the effects of thermal preconditioning on tendon adhesion by regulating the expression of heat shock protein 72 (HSP72) in rat models. METHODS: Sixty male Wistar rats were collected and randomly assigned into the thermal preconditioning and control groups. During the 4th and 8th weeks following surgery, 15 rats were sacrificed in each period respectively, and their tendon adhesion was observed and evaluated. Biomechanical testing was performed to measure the tensile strength and gliding distance of tendons. Hematoxylin-eosin (HE) was used to observe the morphological structure of the tendons. Immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the HSP72, fibroblast growth factor-2 (FGF-2), fibroblast growth factor receptor-1 (FGFR-1), ß-catenin, epithelial cell adhesion molecule (EPCAM), Tenomodulin and scleraxis protein expressions. Pearson correlation analysis was applied to analyze the correlation between HSP72 expression and tendon adhesion. RESULTS: At the 4th week after surgery, we found no differences in the tendon adhesion scores or mRNA and protein expressions of HSP72 between the thermal preconditioning and control groups. However, after the 8th week after surgery, the thermal preconditioning group had a lower tendon adhesion score and higher mRNA and protein expressions of HSP72 than the control group. During the same period, we found longer gliding distance and higher expression levels of FGF-2, FGFR-1, ß-catenin, Tenomodulin and scleraxis, but lower EPCAM expression in the thermal preconditioning group. Pearson correlation analysis indicated that HSP72 mRNA and protein expression levels were negatively correlated with tendon adhesion. CONCLUSIONS: These findings provide evidence that thermal preconditioning may alleviate tendon adhesions via upregulation of HSP72 expression.

Early cellular responses of BMSCs genetically modified with bFGF/BMP2 co-cultured with ligament fibroblasts in a three-dimensional model in vitro.

Currently, a number of strategies including the implantation of bone marrow-derived mesenchymal stem cells (BMSCs) and growth factors have been developed to regenerate the tendon-to-bone interface after performing anterior cruciate ligament reconstruction. However, the mechanisms behind the interactions of the implanted BMSCs and tendon cells remain to be elucidated. The aim of this study was to evaluate the early cellular responses of BMSCs genetically modified with basic growth factor growth factor (bFGF)/bone morphogenic protein 2 (BMP2) and ligament fibroblasts in a three-dimensional co-culture model. BMSCs and ligament fibroblasts were both isolated from male Wistar rats. The BMSCs were then transfected with an adenoviral vector carrying bFGF or BMP2. The transfected BMSCs and ligament fibroblasts both encapsulated in alginate beads were co-cultured for 6 days in three-dimensional model. On days 0, 3 and 6, cell proliferation was assayed. On day 6, the expression of several tendon-bone related markers was evaluated. In the co-culture system, bFGF and BMP2 were highly expressed at the mRNA and protein level. During the process, bFGF significantly promoted cell proliferation, as well as the expression of scleraxis (SCX) and collagen (COL) type â…  (COL1) in the BMSCs; however, it markedly decreased the expression of phenotype markers in the ligament fibroblasts, including COL1 and COL3. BMP2 markedly increased the expression of alkaline phosphatase and osteocalcin in the BMSCs and ligament fibroblasts, whereas it had no obvious effect on cell proliferation and collagen synthesis in the ligament fibroblasts. The combination of bFGF and BMP2 resulted in the similarly enhanced proliferation of BMSCs and ligament fibroblasts as observed with bFGF alone; however, this combination more potently promoted osteogenic differentiation than did BMP2 alone. The findings of our study demonstrate the superiority of the combined use of growth factors in inducing osteogenic differentiation and provide a theoretical foundation for the regeneration of the tendon-to-bone interface.

Enhancement of tendon-to-bone healing after anterior cruciate ligament reconstruction using bone marrow-derived mesenchymal stem cells genetically modified with bFGF/BMP2.

Many strategies, including various growth factors and gene transfer, have been used to augment healing after anterior cruciate ligament (ACL) reconstruction. The biological environment regulated by the growth factors during the stage of tendon-bone healing was considered important in controlling the integrating process. The purpose of this study was to evaluate the effects of bone marrow-derived mesenchymal stem cells (BMSCs) genetically modified with bone morphogenetic protein 2 (BMP2) and basic fibroblast growth factor (bFGF) on healing after ACL reconstruction. BMSCs were infected with an adenoviral vector encoding BMP2 (AdBMP2) or bFGF (AdbFGF). Then, the infected BMSCs were surgically implanted into the tendon-bone interface. At 12 weeks postoperatively, the formation of abundant cartilage-like cells, smaller tibial bone tunnel and significantly higher ultimate load and stiffness levels, through histological analysis, micro-computed tomography and biomechanical testing, were observed. In addition, the AdBMP2-plus-AdbFGF group had the smallest bone tunnel and the best mechanical properties among all the groups. The addition of BMP2 or bFGF by gene transfer resulted in better cellularity, new bone formation and higher mechanical property, which contributed to the healing process after ACL reconstruction. Furthermore, the co-application of these two genes was more powerful and efficient than either single gene therapy.

Association study between growth differentiation factor 5 polymorphism and non-contact anterior cruciate ligament rupture in Chinese Han population.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is the most common ligamentous injury for active adolescents and young adults each year. However, the precise etiologies of ACL injury are not fully understood. The present study was to investigate +104T/C polymorphism of growth differentiation factor 5 (GDF5) gene in patients with ACL rupture, and evaluate the effects of polymorphism on GDF5 mRNA levels in ligament of patients with ACL rupture in central China. METHODS: A total of 286 Chinese patients with ACL rupture and 500healthy controls were enrolled in this study. The +104T/C polymorphism in GDF5 gene were genotyped by DNA sequencing. GDF5 mRNA expressions levels in ligament were determined by quantitative PCR. RESULTS: The frequency of the TT genotype tended to be higher in ACL rupture group than in control group (62.6% vs. 48.0%, P< 0.001, OR = 1.81, 95% CI: 1.35-2.44). T allele of the GDF5 +104T/C polymorphism was more common in ACL rupture group than in control group (P< 0.001). Patients carrying TT genotype expressed lower levels of GDF5 mRNA than C carriers (P = 0.005) among ACL rupture. CONCLUSION: Our study indicated that GDF5 +104T/C polymorphism was associated with ACL rupture patients in central China. This is likely from decreased expressions of GDF5 mRNA. Further studies are necessary to explore the functional implication of the GDF5 +104T/C polymorphism in Chinese ACL rupture patients.

Angelica sinensis and osteoarthritis: a natural therapeutic link?

The dried root of Angelica sinensis is widely used in Chinese traditional medicine for its beneficial effects against several diseases, including osteoarthritis. In order to understand the mechanism of action, two main components of the plant, the phytochemical, sodium ferulate, and a polysaccharidic fraction have been tested on osteoarthritis animal models or in human chondrocytes stimulated by the pro-inflammatory cytokine, Interleukine-1ß. The results showed that sodium ferulate exhibited marked anti-inflammatory and anti-apoptotic properties by inhibiting the TNF/TNFR signal transduction pathway. On the other hand, the polysaccharidic fraction which contains a mixture of various carbohydrates was found to promote proteoglycan biosynthesis in cartilage matrix by stimulating the activity of the UDP-glycosyltransferases that synthesize the chondroitin sulfate chains of aggrecans. It is suggested that the combined action of sodium ferulate and polysaccharidic fraction would prevent cartilage destruction in osteoarthritis and favor cartilage repair.

Maternal and fetal metabonomic alterations in prenatal nicotine exposure-induced rat intrauterine growth retardation.

Prenatal nicotine exposure causes adverse birth outcome. However, the corresponding metabonomic alterations and underlying mechanisms of nicotine-induced developmental toxicity remain unclear. The aims of this study were to characterize the metabolic alterations in biofluids in nicotine-induced intrauterine growth retardation (IUGR) rat model. In the present study, pregnant Wistar rats were intragastrically administered with different doses of nicotine (0.5, 1.0 and 2.0 mg/kg d) from gestational day (GD) 11-20. The metabolic profiles of the biofluids, including maternal plasma, fetal plasma and amniotic fluid, were analyzed using (1)H nuclear magnetic resonance (NMR)-based metabonomic techniques. Prenatal nicotine exposure caused noticeably lower body weights, higher IUGR rates of fetal rats, and elevated maternal and fetal corticosterone (CORT) levels compared to the controls. The correlation analysis among maternal, fetal serum CORT levels and fetal bodyweight suggested that the levels of maternal and fetal serum CORT presented a positive correlation (r=0.356, n=32, P<0.05), while there was a negative correlation between fetal (r=-0.639, n=32, P<0.01) and maternal (r=-0.530, n=32, P<0.01) serum CORT level and fetal bodyweight. The fetal metabonome alterations included the stimulation of lipogenesis and the decreased levels of glucose and amino acids. The maternal metabonome alterations involved the enhanced blood glucose levels, fatty acid oxygenolysis, proteolysis and amino acid accumulation. These results suggested that prenatal nicotine exposure is associated with an altered maternal and fetal metabonome, which may be related to maternal increased glucocorticoid level induced by nicotine.

Association between severity of knee osteoarthritis and serum and synovial fluid interleukin 17 concentrations.

OBJECTIVE: To determine interleukin (IL)-17 concentrations in serum and synovial fluid from patients with knee osteoarthritis, and evaluate their correlation with disease severity. METHODS: Serum and synovial fluid were collected from patients with primary knee osteoarthritis; age- and sex-matched healthy control subjects provided serum samples. This study was conducted retrospectively. IL-17 was quantified by enzyme-linked immunosorbent assay. Osteoarthritis severity and grade were assessed using the Lequesne index and Kellgren and Lawrence (KL) grading system, respectively. RESULTS: Serum IL-17 concentrations were significantly higher in patients (n = 98) than in controls (n = 50). In the patient group, the synovial fluid IL-17 concentration increased significantly with KL grade and was significantly positively correlated with Lequesne index (r = 0.6232). CONCLUSIONS: The synovial fluid IL-17 concentration could represent a useful biochemical marker to reflect knee osteoarthritis severity and progression.

Effect of Angelica sinensis Polysaccharides on Osteoarthritis In Vivo and In Vitro: A Possible Mechanism to Promote Proteoglycans Synthesis.

This study investigated the effect of Angelica sinensis polysaccharides (APS-3c) on rat osteoarthritis (OA) model in vivo and rat interleukin-1-beta- (IL-1 ß -) stimulated chondrocytes in vitro. APS-3c was administrated into rat OA knee joints and had protective effects on rat OA cartilage in vivo. Primary rat articular chondrocytes were cotreated with APS-3c and IL-1 ß in vitro. 2~50 µ g/mL APS-3c had no effect on chondrocytes viability, whereas it increased the proteoglycans (PGs) synthesis inhibited by IL-1 ß . Microarray analysis showed that the significant changes were concentrated in the genes which were involved in PGs synthesis. RT-PCR confirmed that treatment with APS-3c increased the mRNA expression of aggrecan and glycosyltransferases (GTs) inhibited by IL-1 ß but did not affect the mRNA expression of matrix-degrading enzymes. These results indicate that APS-3c can improve PGs synthesis of chondrocytes on rat OA model in vivo and IL-1 ß -stimulated chondrocytes in vitro, which is due to the promotion of the expression of aggrecan and GTs involved in PGs synthesis but not the inhibition of the expression of matrix-degrading enzymes. Our findings suggest the clinical relevance of APS-3c in the prospective of future alternative medical treatment for OA.

Comparison of functional performance after total knee arthroplasty using rotating platform and fixed-bearing prostheses with or without patellar resurfacing.

OBJECTIVE: To retrospectively compare the functional performances of rotating platform and fixed-bearing total knee arthroplasties with or without patellar resurfacing. METHODS: One hundred and ninety-seven patients (205 knees) of mean age 66.4 years were randomly assigned to receive different prostheses. One hundred ninety-five patients, including 97 fixed-bearing prostheses with 37 patellae resurfaced and 106 rotating platform prostheses with 76 patellae resurfaced, were followed up for a mean duration of 32 months. RESULTS: Outcomes in the rotating platform with patellar resurfacing and fixed-bearing with patellar resurfacing groups did not differ significantly according to Hospital for Special Surgery (HSS) scores and flexion and extension angles. For total knee arthroplasties without patellar resurfacing, there were no significant differences in HSS score and flexion angle between the rotating platform and fixed-bearing subgroups. Although the extension angle of rotating platform prostheses was slightly better than that of the fixed-bearing in the patellar non-resurfacing group, this difference was not clinically significant. CONCLUSIONS: Rotating platform and fixed-bearing prostheses have similar overall postoperative outcomes with regard to postoperative HSS scores and extension and flexion angles. Rotating platform prostheses are not superior to fixed bearing prostheses.

TNF/TNFR signal transduction pathway-mediated anti-apoptosis and anti-inflammatory effects of sodium ferulate on IL-1ß-induced rat osteoarthritis chondrocytes in vitro.

INTRODUCTION: Sodium ferulate (SF) is a natural component of traditional Chinese herbs. Our previous study shows that SF has a protective effect on osteoarthritis (OA). The objective of this study was to investigate the effect of SF on the TNF/TNF receptor (TNFR) signal transduction pathway of rat OA chondrocytes. METHODS: Primary rat articular chondrocytes were co-treated with IL-1ß and SF. Chondrocyte apoptosis was assessed by fluorescein isothiocyanate-annexin V/propidium iodide assay. The PCR array was used to screen the expression of 84 key genes involved in apoptosis. The release of TNFα and prostaglandin E2 were analyzed by ELISA. Expressions of proteins were assessed by western blotting. The activity of NF-κB was determined by electrophoretic mobility shift assay (EMSA). Gene expression of inducible nitric oxide synthase (iNOS) was evaluated by real-time quantitative PCR. The nitric oxide content was measured with the Griess method. RESULTS: After treatment with SF, the apoptosis rate of chondrocytes significantly attenuated (P < 0.01). Results of the apoptosis PCR array suggested that mRNA expression of some core proteins in the TNF/TNFR pathway showed valuable regulation. The protein expressions of TNFα, TNFR-1, TNF receptor-associated death domain, caspase-8 and caspase-3 were prevented by SF in a concentration-dependent manner. SF also inhibited activities of caspase-8 and caspase-3 compared with the OA model control (P < 0.01). TNF receptor-associated factor-2 expression, phosphorylations of inhibitor of NF-κB kinase (IKK) subunits alpha and beta, and NF-κB inhibitor, alpha (IκBα) were all concentration-dependently suppressed by SF treatment. The results of EMSA showed that SF inhibited the activity of NF-κB. In addition, the expressions of cycloxygenase-2 and iNOS and the contents of prostaglandin E2 and NO were attenuated with the treatment of SF (P < 0.01). CONCLUSION: SF has anti-apoptosis and anti-inflammatory effects on an OA model induced by IL-1ß in vitro, which were due to inhibitory actions on the caspase-dependent apoptosis pathway and the IKK/NF-κB signal transduction pathway of the TNF/TNFR pathway.