BACKGROUND:The bone metabolism of osteoarthritis is regulated by estrogen with osteoblasts, osteoclasts and cytokines, as wel as a number of regulatory pathways.
OBJECTIVE:To describe the role of estrogen and estrogen-related compounds for joint protection, repair of bone and cartilage cells, and inhibition of synovitis in osteoarthritis.
METHODS:Author researched PubMed, Embase, Elseveir database from 1992 to 2014, with the key words of“osteoarthritis, estrogens, matrix metal oproteinases, interleukins, tumor necrosis factor-alpha”. After the quality of the included studies was evaluation, valid data were extracted and analyzed.
RESULTS AND CONCLUSION:Estrogen can increase the expression of osteoprotegerin and nuclear factor-κB factor ligands in osteoblasts, inhibit bone resorption, prevent the onset and progression of osteoarthritis. Estrogen upregulates anti-osteoclast cytokines, downregulates pro-osteoclast factors, and contribute to regulate bone metabolism of osteoarthritis patients through bone morphogenetic protein and Wnt signaling. Estrogen promotes the adrenal cortex secretion of glucocorticoids and indirectly inhibits the production of matrix metal oproteinases by the hypothalamus-hypophysis-adrenal gland axis. Exogenous estrogen inhibits bone resorption, which may help to delay the development of osteoarthritis. Estrogen and estrogen-related compounds may inhibit the cartilage loss caused by synovitis and inflammatory factors in the late stage of osteoarthritis.

When insonated with fundamental frequency, the ultrasound contrast microbubbles are able to produce nonlinear scattering and generate nonlinear frequencies. The nonlinear properties of these microbubbles can be used to create nonlinear imaging modality and significantly improve the diagnostic capability of medical ultrasound. This paper was a review about the current research progress of nonlinear properties of ultrasound contrast microbubbles and nonlinear imaging, especially about the nonlinear properties under different frequency, acoustic pressure and the application of nonlinear imaging. A prospect of the future research and application was finally put forward in the paper.

BACKGROUND:Mesenchymal stem cel s can differentiate into nerve cel s by chemical induction or co-culture method, but whether mesenchymal stem cel s co-cultured with Schwann cel s differentiate into neuronal-like cel s or Schwann-like cel s is stil controversial.
OBJECTIVE:To explore the inductive role of Schwann cel s derived from rats in the differentiation of human umbilical cord mesenchymal stem cel s.
METHODS:Cocultures of human umbilical cord mesenchymal stem cel s (1×109/L) and Schwann cel s (1×109/L) from neonatal rats were performed using transwel culture dishes. After 2 weeks of cocultures, morphology of the cultured human umbilical cord mesenchymal stem cel s was observed, and the phenotypic changes of cel s were also detected with immumocytochemistry techniques.
RESULTS AND CONCLUSION:After 2 weeks of cocultures, some differentiated cel s showed neuron-like morphology, and expressed nestin, NF-200 andβ-III-tubulin, but did not express Schwann cel special marker S100 and oligodendrocytes special marker MAB1580. These findings indicate that human umbilical cord mesenchymal stem cel s can transdifferentiate into neuronal-like cel s by cocultures with rat’s Schwann cel s.

Objective To investigate the origin of α-SMA positive cells in the outflow tract ridge of the embyonic mouse heart and to explore the ultrastructure change of the mesenchymal cells during the ridges fusion. Methods Sections of embryonic day 10(E10d) to E14d mouse embryonic hearts were stained by immunohistochemistry assay with monoclonal antibodies against α-smooth muscle actin (α-SMA), α-sarcomeric actin(α-SCA) and in situ hybridization method with PlexinA2 probe. The outflow tract ridges fusion was observed by transmission electron microscopy at E12.5d. Results From E10d to E11d, PlexinA2 positive cells were seen in the neural tube with mesenchymes around it, the aortic sac and aortic arch. These cells also migrated into the outflow tract ridge along the aortic sac wall and part of them expressed α-SMA. At E12d, PlexinA2 was expressed in the spinal ganglia, the pharyngeal mesenchyme, the aorto-pulmonary septum and the ascending aorta and pulmonary trunk. The septum showed α-SMA strongly positive. But only a few of α-SMA positive cells were observed in the ascending aorta and pulmonary trunk. At E12.5d, two clusters of condensed mesenchymal cells in the outflow tract ridges formed and began to express PlexinA2 weakly and α-SMA strongly. When the ridges began to fuse, the endothelial cells formed a cellular seam, which rapidly broke into pieces and disappeared and were replaced by the sparsed mesenchymal cells containing a few of microfilaments. Two clusters of condensed mesenchymal cells gradully moved to merge. It was noted that some mesenchymal cells contained plenty of microfilament bundles, mitochondria and focal contacts between them. Some mesenchymal cells only had a few of microfilaments and plasma membrane fusion was seen between them. Conclusionα-SMA positive cells in the outflow tract cushion may be derived from cardiac neural crest. The endothelial cells might participate in the fusion of the outflow tract ridges by endothelial-mesenchymal transformation. Mesenchymal cells of the condensed cell mass contain plenty of microfilament bundles and focal contacts or membrane fusion, which contribute to the ridges fusion.

BACKGROUND: A novel biodegradable Mg-Zn alloy is designed which the density and the Young's modulus are proximal to human bone. At the same time, it depletes the toxicity of aluminium and rare earth element in commercial magnesium alloys. OBJECTIVE: To observe the effect of Mg-Zn alloy (Mg-6%Zn) on the integrin βi expression of preosteoblasts MC3T3-E1. DESIGN, TIME AND SETTING: A contrast study was performed at the Central Laboratory of the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University between March and May 2008. MATERIALS: The Mg-6% Zn was prepared by School of Materials Science and Engineering of Shanghai Jiao Tong University, which the density was 1.82 g/cm~3 and the Young's modulus was nearly 44 GPa. Poly-L-lactic acid (PLLA) was used as the controls. MC3T3-E1 cells were provided by Chinese Academy of Science Type Culture Collection. METHODS: The cell attachment was observed after cultured with Mg-Zn and PLLA at 2, 24 and 48 hours under scanning electron microscope; the integrin β1 mRNA expression of MC3T3-E1 cultured with Mg-Zn and PLLA was estimated by real-time fluorescent quantitative polymerase chain reaction (real-time PCR) at days 1, 3, 6, 9,12 and 15 after culture. MAIN OUTCOME MEASURES: The MC3T3-E1 cells attachment on the material surface and the integrin β1 mRNA expression. RESULTS: MC3T3-E1 cell adhesion was better on the Mg-Zn alloy surfaces than on the PLLA surface; The integrin (31 mRNA of osteoblasts on Mg-Zn kept on expressing during experiment and increased with time (P < 0.01), but there was no significantly difference between the two groups at the same time (P > 0.05). CONCLUSION: MC3T3-E1 cell adhesion is better on the Mg-Zn alloy surfaces than on the PLLA surface, but it is not mediated by inducing the integrin p1 mRNA expression.

Objective To investigate the spatiotemporal expression patterns of transforming growth factor-β(TGF-β) receptors type Ⅰ and type Ⅱ and their relationships with development of outflow tract(OFT) in mouse embryonic heart. Methods Serial sections of mouse embryos from embryonic day 9 (E9d) to embryonic day 14 (E14d) were stained using PAP immunohistochemical methods. Results Expressions of TGF-β receptors type Ⅰ (TGF-βRⅠ) and type II(TGF-βRⅡ) in the myocardial wall of OFT started at E10d, reached the reflection with splanchnic epithelium on the dorsal wall of the pericardial cavity at E11d. At E12d, expression intensity of TGF-βRⅠ and TGF-βRⅡ in myocardium increased to its highest level, and TGF-βRⅡ positive mesenchymal cells in OFT ridges could be detected. After E13d the staining intensity of TGF-βRⅠ and TGF-βRⅡ decreased rapidly,and at E14d,their expressions had fallen at the lowest.Conclusion The expressions of TGF-βRⅠ and TGF-βRⅡ in OFT are confined to the period of E10d to E14d, they may play important roles in regulating the myocardial cell proliferation, remodeling and septation of OFT, and promoting the differentiation from mesenchymal cells in the secondary heart field into smooth muscle cells in the distal end of OFT.

Objective To investigate the role of intestinal fatty acid binding protein(I-FABP)in evaluating intestinal dysfunction of septic rats and the effect of glutamine on I-FABP expression.Methods Rats were divided into 3 groups,control group were only fed with Peptisorb,model group were fed with Peptisorb after intraperitoneal injection with E.coli endotoxin lipopolysaccharidegiven and glutamine group were added glutamine on basis of model group.The correlation between serum I-FABP level and intestinal mucosa damage index were analyzed and the concentrations of serum I-FABP in each group were observed and compared. Results The serum level of I-FABP in rats were correlated with the Chiu’s score of intestinal mucosa,mucosa thickness and villus length(P<0.05 ).Compared with control group,the concentration of serum I-FABP in model group and glutamine group were significantly increased(P<0.05),but which in glutamine group was lower than that in model group(P<0.05).Conclusions Serum I-FABP could be an non-invasive diagnosis index for evaluating acute intestinal dysfunction in septic rats.In addition,dietary glutamine supplementation may ameliorate sepsis-induced intestinal epithelial injury in rats.

BACKGROUND:Mechanical, inflammatory, and biochemical factors, particularly matrix metaloproteinases and reactive oxygen lead to chondrocyte degeneration in osteoarthritis. Curcumin has been shown to be a potent antioxidant; however, its protective effects against chondrocyte degeneration in osteoarthritis remain unclear.
OBJECTIVE:To investigate the potential molecular mechanisms underlying the protective effects of curcumin on articular cartilage of osteoarthritis in rats.
METHODS:A total of 30 Sprague-Dawley rats were used and randomly divided into model group (positive control,n=15) and normal group (negative control,n=15). Rat models of traumatic osteoarthritis were established, and then cartilage cels were isolated from articular cartilage and culturedin vitro. Chondrocytes were treated with curcumin (curcumin group) or PDTC (an inhibitor of nuclear factor-kappa B) for 24 hours. The expression level of nuclear factor-kappa B P65 in nucleus and cytoplasm in chondrocytes were determined by western blot assay and immunofluorescence. Moreover, mRNA expressions of type II colagen, matrix metaloproteinase-1 and -13 were analyzed using RT-qPCR.
RESULTS AND CONCLUSION: Nuclear factor-kappa B P65 protein was mainly expressed in nucleus, but few in cytoplasm in positive control group; the reversed results were found in the curcumin group. Nuclear translocation of nuclear factor-kappa B P65 was observed mainly in nucleus in the positive control group; however, that was observed mainly in cytoplasm in the negative control, curcumin, and PDTC groups. Matrix metaloproteinase-1 and -13 mRNA expressions were significantly decreased, while type II colagen mRNA expression was significantly increased in the curcumin group compared with the positive control group. These findings indicated that curcumin protect chondrocytes against degeneration through inhibiting the activation of nuclear factor-kappa B signaling pathway, suppressing nuclear translocation of nuclear factor-kappa B P65 and inhibiting the expressions of matrix metaloproteinase-1 and -13, which are responsible for upregulation of type II colagen expression.

AIM: To study the effect of calcium sensing receptor (CaSR) on icariin (ICA) induced mouse embryonic stem cells ( mESCs) to differentiate into cardiomyocytes in vitro.METHODS:mESCs were cultured to embry-oid bodies ( EBs) by direct suspension method and the differentiation of EBs into cardiomyocytes was induced by ICA.The expression of cardiac specific proteinsα-actinin and cardiac troponin-I ( cTnI) was analyzed by Western blot and immuno-fluorescence.The differentiation rate was determined by flow cytometry.The ultrastructure of the derived cardiomyocytes was further characterized by transmission electron microscopy.The expression of cardiac-specific transcription factors Nkx2.5 and GATA-4,as well as CaSR was detected by Western blot.RESULTS: After induction with ICA, the positive characteristics of myocardial cells appeared in the EBs cultured for 2 d.The expression of cardiac-specific sarcomeric pro-tein actinin (α-actinin) and cTnI showed an overall upward trend by Western blot in different phases of ICA induced differ-entiation.The expression of CaSR, Nkx2.5 and GATA-4 was the highest at an early stage of ICA-induced differentiation. Neomycin (an activator of CaSR) up-regulated CaSR, NKx2.5 and GATA-4 expression in the EBs at early stage of ICA-in-duced differentiation, all of which were reversed by NPS2390 ( an inhibitor of CaSR) .CONCLUSION:CaSR is function-ally expressed in mESC-derived cardiomyocytes, and activation of CaSR is involved in the differentiation of mESCs into car-diomyocytes by facilitating the expression of NKx2.5 and GATA-4.

BACKGROUND:Intra-articular injection of sodium hyaluronate or dexamethasone can relieve pain and increase range of motion after traumatic arthritis. OBJECTIVE:To observe the effect of dexamethasone combined with sodium hyaluronate on traumatic arthritis of rat knees. METHODS:Forty-eight Sprague-Dawley rats were randomly divided into four groups. The anterior ligament of the left knee was resected and the medial meniscus was removed to establish models of traumatic arthritis in al the rats. After 3 weeks, the four groups were respectively injected dexamethasone+sodium hyaluronate (combined group), dexamethasone, sodium hyaluronate, and nothing (control group). After 4, 8, 12 weeks of injection, the samples were obtained for gross observation, anteroposterior and lateral X-ray films and hematoxylin-eosin staining. RESULTS AND CONCLUSION:At 12 weeks after injection, X-ray films showed that there was no stenosis in the combined group, mild stenosis in the dexamethasone and sodium hyaluronate groups, and obvious stenosis in the control group (indicating severe osteoarthritis);hematoxylin-eosin staining exhibited the fibrous cartilage-like tissue grew wel in the combined group, varying degrees of proliferation of fibrous cartilage-like cells were visible in the dexamethasone and sodium hyaluronate groups, and there was a smal amount of fibrosis in the control group. These findings suggest that the combination of dexamethasone and sodium hyaluronate can improve the cartilage repair and restore the joint function.