TLR2 is expressed in human articular cartilage and is upregulated by proarthritic agents including IL-1beta and fibronectin fragments. Signaling through TLR is a novel pro-inflammatory mechanism in osteoarthritis and targeting of these signaling pathways may be of value in treatment of degenerative joint disease.

No abstract

We aimed to establish an animal model to investigate primary osteoarthritis of the lumbar facet joints after collagenase injection in rats and its effects on chondrocyte apoptosis. We hypothesized that osteoarthritic-like changes would be induced by collagenase injection and that apoptosis of chondrocytes would increase. Collagenase (1, 10, or 50 U) or saline (control) was injected into the lumbar facet joints. The histology and histochemistry of cartilage, synovium, and subchondral bone were examined at 1, 3, and 6 weeks after surgery. Apoptotic cells induced by 1 U of collagenase were quantified using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay. Degeneration of the cartilage and changes to the synovium and subchondral bone were dependent on both the doses of collagenase and the time after surgery. There were significantly more apoptotic chondrocytes in collagenase-treated joints than in control (P < 0.001 at 1 and 3 weeks and P < 0.05 at 6 weeks). Thus, lumbar facet joints subjected to collagenase developed osteoarthritic-like changes that could be quantified and compared. This model provides a useful tool for further study on the effects of compounds that have the potential to inhibit enzyme-associated damage to cartilage.

These findings implicate these six genes in the development of glomerular crescents. More importantly, detection of Sparc, OPN and Lcn2 in urine may mean that these molecules could serve as important biomarkers for non-invasive diagnosis of glomerular crescents.

ErbB2 (HER2/neu) is overexpressed in about 25-30% of breast malignancies, and up-regulation of ErbB2 in breast cancer patients is associated with poor prognosis. It is known that the carboxyl terminus of heat shock cognate 70 interacting protein (CHIP) efficiently down-regulates ErbB2 in vitro. Human tumourous imaginal disc 1 (Tid1, DnaJa3), a co-chaperone of heat shock protein 70 (Hsp70), also suppresses ErbB2 expression in breast cancer cell lines. However, the intracellular interactions among Tid1, CHIP, and ErbB2 remain elusive, and the utilization of Tid1 and CHIP as breast cancer biomarkers has never been proposed. Herein, we analysed the expression and correlations among Tid1, CHIP, and ErbB2 in a total of 183 breast cancer histology sections, including 30 fresh tissue specimens, using immunohistochemistry (IHC) and immunoblotting assay. A computerized image analysis system was used for IHC scoring and determining relative immunoblot intensity. The immunohistochemical expression of Tid1 and CHIP were positively correlated with each other but were both inversely correlated to that of ErbB2. Odds ratio analyses showed that lower expression of Tid1 has a relatively higher risk of unfavourable tumour grade, later pathological stage, larger tumour size, and microscopic features of a more malignant histology including lymphovascular invasion, stromal inflammatory response, and tumour necrosis. Expression of CHIP displayed similar characteristics. Furthermore, expression of Tid1 and/or CHIP increases patients' 10-year overall and disease-free survival rate. Empirically, we also demonstrated that Tid1, CHIP, and ErbB2 interacted with each other through immunofluorescence or co-immunoprecipitation analyses. Functionally, Tid1 and CHIP acted synergistically to degrade ErbB2 in vitro. Conversely, Tid1 cannot compensate for the loss of proteolytic function noted in CHIP mutations for degradation of ErbB2. Overall, our data suggest that Tid1 and CHIP play pivotal roles in affecting the levels of ErbB2 protein, and that both are significant prognostic indicators of breast cancer patient survival.

Aberrant beta-catenin expression may play an important role in the histologic differentiation and tumor staging of MEC.

No abstract

Hyperphosphatemia induces endothelial autophagy, possibly through the inhibition of the Akt/mTOR signaling pathway, which may play a protective role against high Pi-induced apoptosis.