This study aimed to determine the effect of fibronectin (FN) on cartilage regeneration through the activation of chondrogenic progenitor cells (CPCs). Cells were isolated from the knee cartilage of mice and cultured in the presence of various concentrations of FN. Proliferation, migration, and chondrogenic differentiation assays were performed in vitro. In some experiments, CPCs were preincubated with anti-integrin α5β1 antibody for 60 min before FN treatment to block the integrin α5β1 receptor. Soluble FN was mixed with Pluronic F-127 and injected into the joint cavity in an early-stage osteoarthritis model. Cartilage repair was evaluated histologically, biochemically, and biomechanically. In vitro, we observed that the isolated CPCs, which exhibited stem cell-relevant markers, proliferated most at a concentration of 20 μg/mL FN (p < 0.05). In addition, FN enhanced the proliferation, migration, and chondrogenic differentiation capacity of CPCs, and the enhancement was significantly decreased by blockade of the integrin α5β1 receptor (p < 0.05). In vivo, FN also significantly promoted cartilage repair along with increased CPC activation and integrin α5β1 expression (p < 0.05). These findings suggest that FN enhances CPC proliferation, migration, and chondrogenic differentiation through the integrin α5β1-dependent signaling pathway. Based on these results, a novel and promising therapy focused on targeted activation of CPCs by FN could be developed for the treatment of cartilage injuries in a clinical setting.
Purpose. The purpose of this study is to investigate whether double-row suture technique is a better option for the treatment of Haglund syndrome than single-row suture technique regarding the surgical outcomes. Methods. Thirty-two patients with Haglund syndrome were recruited in this study. Patients were divided into Group 1 (treated with single-row suture technique) and Group 2 (treated with double-row suture technique). There were 16 patients in each group. The AOFAS-ankle-hindfoot scale, VISA-A scores, and Arner-Lindholm standard were used to assess the clinical outcomes. The pre- and postoperative X-rays were used to assess the radiological outcome. Results. Both AOFAS-ankle-hindfoot scale score and VISA-A score had varying degrees of improvement in both groups. In latest follow-up assessment, the Arner-Lindholm standard investigation showed there were 7 excellent, 7 good, and 2 bad outcomes in Group 1 and 12 excellent and 4 good outcomes in Group 2. In Group 2 patients, there were no more posterosuperior bony prominence of the calcaneum in post-op X-rays and there were no recurrent cases. The ankle-related scale score was statistically significantly higher in Group 2 than in Group 1 (P = 0.029). Conclusion. The double-row suture technique seems to be a better option to treat Haglund syndrome than single-row suture technique.
Aims: Opening of the mitochondrial permeability transition pore (mPTP) is a critical event during ischemia/reperfusion (I/R) injury. Recently, we showed that Panax quinquefolium saponin (PQS) alleviates apoptosis of cardiomyocytes by suppressing excessive endoplasmic reticulum stress (ERS) during I/R injury. Here, we hypothesized that this anti-apoptotic effect might be mediated through inhibition of mPTP and the mitochondrial apoptotic pathway. Methods: Ninety-six healthy male Sprague-Dawley rats were randomly divided into sham, I/R, I/R+PQS (200 mg/kg/d), Cyclosporine A (CsA, 10 mg/kg), I/R+CsA (10 mg/kg), and I/R+PQS+CsA. I/R was modeled in rats by ligating the left anterior descending artery (LAD) for 30 min followed by 120 min of reperfusion. To evaluate the cardioprotective function of PQS, we measured hemodynamics, serum content of creatine kinase-MB (CK-MB), myocardial infarct size, and myocardial apoptotic index (AI). We investigated the underlying mechanism by examining changes in the mitochondrial ultrastructure and membrane potential (ΔΨm), dynamics of mPTP opening, expression of cleaved caspase-3, cleaved caspase-9 in the myocardium, Bcl-2 and Bax in the mitochondria versus cytosol, and translocation of cytochrome c. Results: Administration of PQS to I/R rats significantly reduced serum CK-MB level, infarct size and AI. In addition, PQS protected the mitochondrial structure, markedly inhibited mPTP opening and ΔΨm depolarization, led to upregulation of Bcl-2 and downregulation of Bax in the mitochondria compared to the cytosol, and suppressed the expression of cleaved caspase-9 and cleaved caspase-3, as well as I/R induced translocation of cytochrome c to the cytoplasm. Conclusion: Our results show that PQS can alleviate apoptosis of cardiomyocytes during I/R injury, possibly due to repressed mitochondrial apoptotic pathway associated with the opening of mPTP induced by myocardial I/R injury.
The purpose of this study was to establish a partial-thickness articular cartilage defects model in adult rats and explore the respond of chondrogenic cells to the cartilage injury. Forty-five adult Sprague-Dawley rats were divided into operated group, sham-operated group and control group. Partial-thickness cartilage defects were created on the weight-bearing region of femoral condyles by a converted ophthalmic knife. Rats were exposed to 5-bromo-2'-deoxyuridine (BrdU) for five consecutive days and were sacrificed 1, 2 and 4 weeks after surgery. Evaluations of macroscopic and histological changes were made. Chondrocyte apoptosis was evaluated by TUNEL assay. Immunofluorescence staining of CD105 and BrdU, double staining of CD105/integrin α5β1 and CD105-positive cells counting were performed for evaluations of cells around the defects. Cartilage softening and fibrillation with chondrocyte apoptosis were observed around the injury site after surgery. Results of histological scores indicated no significant difference between one time point and a successive time point for either group. CD105-positive cells and BrdU-label-retaining cells were observed around the linear injury. And cells counting showed the number of CD105-positive cells increased at later time points (P < 0.05). Immunofluorescence double staining demonstrated co-localization of CD105 and integrin α5β1 in activated cells around the defects. We establish a partial-thickness cartilage defects model in adult rats and demonstrate this injury may lead to activation of putative progenitor cells. In addition, the activated cells express integrin α5β1 specially, which may help in early discovery of osteoarthritis.
Coronary heart disease (CHD) remains the leading cause of morbidity and mortality worldwide. Traditional Chinese medicine (TCM) is one of the effective complementary and alternative therapies used to improve the prognosis of CHD patients. Xuefu Zhuyu (XFZY) decoction, a classical traditional Chinese medication for regulating Qi and promoting blood circulation, has a clinical benefit in CHD; however, the underlying mechanism is not clear. Recently, it was found that the metabolites involved in amino acid metabolism and the tricarboxylic acid cycle were altered in CHD patients with Qi and Yin deficiency syndrome. To understand the material foundation of Qi, it is of great significance to study the differential metabolites involved in Qi during treatment of CHD with Qi-regulating and blood-promoting herbs. In this study, we investigated the metabolic profiles of serum in CHD patients by nontargeted metabolomics analysis to detect differential metabolites between the XFZY decoction group and placebo group. Ten CHD patients were enrolled and treated with placebo granules or XFZY decoction granules in a random and double-blind manner. Serum samples of all patients were evaluated by untargeted high-performance liquid chromatography with tandem mass spectrometry-based metabolomics. In total, 513 metabolites were detected in the serum of CHD patients, and six of these metabolites participating in seven metabolic pathways were significantly different between CHD patients treated with XFZY decoction and the placebo group. Among the six differential metabolites, FA (20:2)-H and tetracarboxylic acid (24:0), involved in fatty acid metabolism; cis-aconitic acid, which participates in the tricarboxylic acid cycle; 2-deoxy-D-glucose, involved in glucose metabolism; and N-acetylglycine, involved in amino acid metabolism, were decreased, whereas spermine, which participates in amino acid metabolism, was increased as compared with the placebo group. Our findings, combined with the perspective of biological functions, indicate that 2-deoxy-D-glucose and spermine might constitute the partial material foundation of Qi in CHD patients treated with XFZY decoction.
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