An alternative spliced transcript of ADAMTS4 is present in human synovium from OA patients

The major proteoglycan of articular cartilage aggrecan is a substrate for ADAMTS4. RT-PCR analysis of human osteoarthritic (OA) synovial co-cultures using oligonucleotide primers designed to amplify across the exon 8/9 junction of human ADAMTS4 resulted in the amplification of two products, the expected product and a smaller product missing 161 bp from the 5′ end of exon 9, the result of alternative splicing in which exon 8 joins to a cryptic 3′ splice site within exon 9. The protein produced would be identical to human ADAMTS4 up to Arg696, and would have a new C-terminal domain with no commonality with the ADAMTS4 spacer domain. Changes in the C-terminal domain of ADAMTS4 may alter its substrate specificity.