No abstract

pivotal role in chondrodysplasias caused by mutations in cartilage extracellular matrix proteins. The aims of the studies I will present were therefore: i) to characterise the role of chondrocyte ER stress in osteoarthritis; and ii) to demonstrate the clinical potential of alleviating ER stress in an ER stress-related cartilage pathology. Methods: DMM was performed on 10e12 weeks old mice that experienced elevated chondrocyte ER stress due to the chondrocyte-targeted expression of an ER-stress inducing transgene (ColIITgcog). The onset and development of OA was assessed in control and ColIITgcog mice at 2e8 weeks after operation. All histology was assessed in a blinded manner by 3 separate scorers using the Osteoarthritis Research Society International (OARSI) semi-quantitative scoring system for murine OA. Immunohistochemistry was performed on 95% ethanol/5% acetic acid fixed sections and in situ hydridisation using DIG labelled RNA probes. TUNEL assays were performed using a fluorometric TUNEL kit. Cell culture assays of ER stress were performed by qRT-PCR using transiently transfected HeLa cells expressing mutant forms of collagen X and treated with a variety of ER stress reducing drugs. In vivo tests were performed on the mutant pN617K.Col10a1 mouse line. Results and conclusions: I will present data to illustrate that i) increased ER stress is an early event in the development of OA in DMM; ii) chondrocyte apoptosis is an early event in disease onset; iii) increased capacity to cope with ER stress can delay disease onset; however, iv) ER stress does not appear to play a pivotal role in disease progression; v) increased ER stress can be pharmacologically reduced in a number of ways; vi) alleviating ER stress in chondrocytes in vivo can significantly reduce disease severity in an ER-stress related condition.

The CuCl-catalyzed reaction of aryl boronic acid with carbon dioxide to form carboxylate ester after treatment with CH 3 I has been developed. The procedure featured mild conditions and good functional group tolerances. A diverse range of aryl boronic acids were effectively converted into carboxylate esters. Even those bearing sensitive groups such as carbonyl, ester, and amide could produce the desired products in good yields.