Procollagen II amino propeptide processing by ADAMTS-3 - Insights on dermatosparaxis

The amino and carboxyl propeptides of procollagens I and Il are removed by specific enzymes as a prerequisite for fibril assembly. Null mutations in p rocollagen I N-propeptidase (ADAMTS-2) cause dermatosparaxis in cattle and the Ehlers-Danlos syndrome (dermatosparactic type) in humans by preventing proteolytic excision of the N-propeptide of procollagen I. We have found th at procollagen II is processed normally in dermatosparactic nasal cartilage , suggesting the existence of another N-propeptidase(s). We investigated su ch a role for ADAMTS-3 in Swarm rat chondrosarcoma RCS-LTC cells, which fai l to process the procollagen II N-propeptide. Stable transfection of RCS-LT C cells with bovine ADAMTS-2 or human ADAMTS-3 partially rescued the, proce ssing defect, suggesting that ADAMTS-3 has procollagen II N-propeptidase ac tivity. Human skin and skin fibroblasts showed 30-fold higher mRNA levels o f ADAMTS-2 than ADAMTS-3, whereas ADAMTS-3 mRNA was 5-fold higher than ADAM TS-2 mRNA in human cartilage. We propose that both ADAMTS-2 and ADAMTS-3 pr ocess procollagen II, but ADAMTS-3 is physiologically more relevant, given its preferred expression in cartilage. The findings provide an explanation for the sparing of cartilage in dermatosparaxis and, perhaps, for the relat ive sparing of some procollagen I-containing tissues.