Alternative splicing of the G3 domain of aggrecan in osteoarthritic canine articular cartilage

The G3 domain of aggrecan, which is subject to alternative splicing, is composed of one or two EGF-like modules (E1 or E2), a lectin-like module (L), a complement regulatory protein-like module (C) and a C-terminus. The purposes of this project were to study the G3 domain of canine aggrecan by cloning and sequencing the cDNA of the G3 domain and portion of the 3;The cDNA sequence of the canine G3 domain has 91% to 74% homologous with the G3 domain of human, bovine, rat and chicken aggrecan. A putative "aggrecanase" cleavage site (VSQELAQR) exists in the CS-II region and is very similar to the site found at leucine residue 1939 (VSQE;The G3 isoforms were quantified by RT-PCR using total RNA from cartilage of adult stifles in the hypertrophic stage of experimental OA and the contralateral non-operated control (NOP). Expression of the LC isoform was significantly increased when comparing the OA to the NOP by Student's t-test (p ;In conclusion, the G3 domain of aggrecan is conserved in five species compared. The same types of the G3 isoforms were expressed in all the canine articular cartilage investigated. The LC isoform was predominantly expressed in all the cartilage samples tested. The putative G3-containing peptide cleaved by "aggrecanase" and the increase of the ELC isoform in OA may be physiological and pathological significant in the normal and osteoarthritic cartilage.