Osteogenesis imperfecta (lethal) bones contain types III and V collagens.

Abstract

SUMMARY Lethal osteogenesis imperfecta (OI-L) and normal fetal bones contain types I and V collagen with relatively more type V in OI-L bones. The latter, unlike normal fetal bone, also contain some type III collagen. Such altered collagen ratios could directly produce the bony fragility and radiotranslucency of OI-L bones. Since this is an inherited osteoporosis similar alterations in acquired osteoporoses are also possible.Osteogenesis imperfecta (01) (0I-L). They fulfilled the clinical and radiological criteria of fatal short-limbed dwarfism with abnormally broad, undercalcified bones (Fig. 1). Control bones were obtained from five normal fetuses of between 16 and 39 weeks' gestation. The bones were finely minced with a scalpel and decalcified in 0 5 M EDTA, pH 7 6, for 48 hours at 40C. After spinning at 2000 g for 30 minutes and resuspension in 0 5 M acetic acid, pepsin (Worthington) was added to 10% wet weight of bone and digested for 16 hours at 15°C.9 The reaction was stopped by raising the pH to 8-0 for 30 minutes and then desalted by dialysis against 0-5 M acetic acid and Iyophilised. Aliquots were taken for analysis of whole collagen chains and cyanogen bromide peptide mapping. Whole chains were examined on 5% polyacrylamide gels in tris borate SDS at pH 8.6,10 and cyanogen bromide peptides were separated by tube or slab gel electrophoresis using either tris borate SDS at pH 8.610 or SDS phosphate at pH 7-2.11Bacterial collagenase digestion of whole collagen chains (Clostridial Collagenase BDH) was carried out at 37°C for 16 hours in 0-2 M NH4HCO3 and CaC12, pH 8.6.12

Immunohistochemical localization of interstitial collagens in bone tissue from patients with various forms of osteogenesis imperfecta

“…The presence of collagen I11 within bone matrix, especially, confirmed by previous biochemical data [Pope et al, 1980;Kirsch et al, 19871, resembles the staining pattern of immature primary osteoid which occurs during normal fetal ossification and which contains also considerable amounts of collagen 111. Collagen V is confined to the pericellular matrix and does not occur in the bone matrix itself.…”

An unusual pattern of peptide-bound lysine metabolism in collagen from an infant with lethal perinatal osteogenesis imperfecta.

“…A recent review contains brief reference to a study on a type II 01 infant in which a decreased level of hydroxylysine was observed for bone collagen chains (2). Yet other studies on lethal perinatal 01 bone have revealed a small but significant increase in the levels of type III and V collagens in the bone matrix (9). And finally, studies on skin fibroblasts derived from a type II 01 infant have revealed a marked diminution in the ratio of type I/type III procollagen production (10).…”

The Relative Amounts of the Collagen Chains α1(I), α2 and α1(III) in the Skin of 31 Patients with Osteogenesis Imperfecta

“…Abnormal ratios have also been reported by Cole & Bean (1980) by direct examination of the skin. Others have reported over hydroxylation of the lysyl residues in bone collagen (Trelstad, Rubin & Gross, 1977) or an excess of type V collagen (Pope, Nicholls, Eggleton, Narcissi, Hey & Parkin, 1980), which is normally present in bone only at much earlier stages of foetal development (P. K. Muller, personal communication in methods used, these variable results must suggest that the lethal (type II) form of osteogenesis imperfecta includes different biochemical disorders with a very similar presentation.…”