Defects of type I procollagen metabolism correlated with decrease of prolidase activity in a case of lethal osteogenesis imperfecta

We have studied the structure and metabolism of type I procollagen in a cas e of perinatal lethal osteogenesis imperfecta (OI) type II. Cultured skin f ibroblasts from the proband synthesized both normal and abnormal forms of t ype I procollagen. Some abnormal, overmodified molecules were secreted by O I cells, although less efficiently than normal molecules from control cells . The OI fibroblasts accumulated large amounts of abnormal pro alpha1(I) an d pro alpha2(I) chains intracellularly. The extracellular collagenolytic ac tivity was decreased compared to control cells. Furthermore, OI cells produ ced less type I procollagen and demonstrated lower capacity to synthesize D NA than control cells. We have found that in contrast to prolinase activity , the activity of prolidase tan enzyme essential for collagen synthesis and cell growth) is also significantly reduced in OI cells. No differences wer e found in the amount of the enzyme protein recovered from both the OI and control cells. However, we found that expressions of beta1 integrin and ins ulin-like growth factor-I receptor (receptors known to play an important ro le in up regulation of prolidase activity) were decreased in OI cells compa red to control cells. The decrease in prolidase activity may provide an imp ortant mechanism of altered cell growth and collagen metabolism involved in producing the perinatal lethal form of the OI phenotype.