Inflammation induction of Dickkopf-1 mediates chondrocyte apoptosis in osteoarthritic joint.

OBJECTIVE: Dysregulated Wnt signaling appears to modulate chondrocyte fate and joint disorders. Dickkopf-1 (DKK1) regulates the pathogenesis of skeletal tissue by inhibiting Wnt actions. This study examined whether DKK1 expression is linked to chondrocyte fate in osteoarthritis (OA). METHOD: Articular cartilage specimens harvested from nine patients with knee OA and from six controls with femoral neck fracture were assessed for DKK1, interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), Bad, Bax, Bcl2 and caspase-3 expression by real time-polymerase chain reaction (RT-PCR) and immunohistochemistry. Apoptotic chondrocytes were detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labelling (TUNEL) and 4', 6-dianidino-2-phenylindole dihydrochloride (DAPI) staining. Human chondrocyte cultures were treated with recombinant IL-1beta and monoclonal DKK1 antibody to determine whether DKK1 impairs chondrocyte survival. RESULTS: Expression of DKK1 correlated with inflammatory cytokine levels (IL-1beta and TNF-alpha expressions), proapoptosis regulators (Bad and caspase-3 expressions) and TUNEL staining in OA cartilage tissues. The IL-1beta induced expressions of DKK1, Bax, Bad and caspase-3-dependent apoptosis of chondrocyte cultures. Neutralization of DKK1 by monoclonal DKK1 antibody significantly abrogated IL-1beta-mediated caspase-3 cleavage and apoptosis and reversed chondrocyte proliferation. Recombinant DKK1 treatment impaired chondrocyte growth and promoted apoptosis. By suppressing nuclear beta-catenin accumulation and Akt phosphorylation, DKK1 mediated IL-1beta promotion of chondrocyte apoptosis. CONCLUSION: Chondrocyte apoptosis correlates with joint OA. Expression of DKK1 contributes to cartilage deterioration and is a potent factor in OA pathogenesis. Attenuating DKK1 may reduce cartilage deterioration in OA.

Valproic acid protects against MPP+-mediated neurotoxicity in SH-SY5Y Cells through autophagy.

Autophagy is a common physiological activity in cells. Studies show that dysregulation of autophagy is involved in the pathogenesis of Parkinson's disease (PD). As a commonly used anti-epileptic drug, valproic acid (VPA) has shown neuroprotective effects in PD. The aim of this study was to explore whether the autophagy induced by VPA involved in the neuroprotective effects in PD cell model. We found that VPA treatment counteracted MPP+-caused autophagic flux impairment. Forthermore, VPA could alleviates apoptosis, reduce reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) loss caused by MPP+. And we also observed that VPA up-regulated the active caspase-3 and Bcl-2/Bax ratio and inhibited cytochrome c (Cyt c) release from mitochondria to the cytoplasm. However, 3-Methyladenine (3-MA) or bafilomycin A1 (Baf-A1), blockers for autophagy, partially weakened the neuroprotective effect of VPA. Our findings suggest that the neuroprotective effect of VPA on neuroblastoma cells may partially result from inducing autophagy and related to the inhibition of the mitochondrial apoptosis pathway.

Molecular interpenetration within the columnar structure of crystalline anilino-beta-cyclodextrin.

A single crystal of mono(6-anilino-6-deoxy)-beta-cyclodextrin was prepared, and its crystal structure was determined by X-ray crystallographic analysis, which clearly revealed that the anilino groups are consecutively included intermolecularly into the adjacent cyclodextrin cavities in the crystal, thus giving rise to a consolidated column, located on a 2(1)-screw axis.

Outcome of calf deep-vein thrombosis after total knee arthroplasty.

We investigated the outcome of deep-vein thrombosis (DVT) in the calf after total knee arthroplasty (TKA) in 48 patients (45 women and three men) by clinical assessment and venographic study between three and four years after surgery. The mean age of the patients was 67.2 +/- 7.7 years (52 to 85) and the mean follow-up was 42.6 +/- 2.7 months (38 to 48). The diagnosis was osteoarthritis in 47 patients and rheumatoid arthritis in one patient. There were 44 calf thrombi, four popliteal thrombi but no thrombi in the femoral or iliac regions. Of the 48 patients, 24 were clinically symptomatic and 24 were asymptomatic. Clinical examination was carried out on 41 patients, of whom 37 underwent ascending venography. Seven were evaluated by telephone interview. No patient had the symptoms or signs of recurrent DVT, venous insufficiency in the affected leg, or a history of pulmonary embolism. No patient had been treated for complications of their DVT. Thirty-six of the 37 venographic studies were negative for either old or new DVT in the affected leg. One patient had residual thrombi in the muscular branches of the veins. Our study shows that deep-vein thromboses in the calf after TKA disappear spontaneously with time. No patient developed a recurrent DVT, proximal propagation or embolisation. Treatment of DVT in the calf after TKA should be based on the severity of the symptoms during the immediate postoperative period.

In vivo degradation and biocompatibility of a new class of alternate poly(ester-anhydrides) based on aliphatic and aromatic diacids.

The degradation, tissue compatibility, and toxicology of a novel class of alternate poly(ester-anhydrides) were assessed in rats. It was observed that the degradation rate of the polymers in vivo was slower than that in vitro. In addition, erosion and intact zone were observed for all the polymers. IR and SEM analysis of the outer erosion and inner intact zone revealed that the outer zone degraded more rapidly than the inner zone. Such results were similar to that in vitro. All the studied poly(ester-anhydrides) produced mild inflammatory reactions and tissue encapsulation by layers of fibroblastic cells in vivo. Observation of liver and kidney tissue by light microscopy suggested the hydrolytic products of the studied poly(ester-anhydrides) had no harmful effects on the normal tissue/organs. In addition, the polymer and the breakdown products were found to be non-mutagenic by examination of micronucleus in bone marrow.