Types I, II and III collagen were isolated from calvarium, skin and cartilage from a patient with recessive lethal osteogenesis imperfecta. the distribution of the various collagen types was normal in all three tissues. The alpha-chains were purified by molecular sieve and ion-exchange chromatography and were found to differ from the corresponding alpha-chains of age-matched controls only in that the alpha 1(I), alpha 2 and alpha 1(III) chains contained higher amounts of hydroxylysine with proportionally less lysine. alpha 1(II) was normal. The excess hydroxylysine residues were all glycosylated in the case of alpha 1(I) chains, but only partly so for the alpha 2 chains. Similar observations were made with collagen from fetuses at various stages of development. In these fetuses, however, the increase in the degree of hydroxylation of lysine in alpha 1(I), alpha 2 and alpha 1(III) varied with age, being highest in the youngest fetus. Seen in the context of embryonic development, the collagen of the patient would correspond to that of a fetus younger than 18 weeks, and one could speculate that the defect seen in this patient is the result of a disturbed process of maturation of connective tissue.

Purified antibodies against type IV collagen and laminin were used ot localize basement membranes by indirect immunofluorescence in various anatomical regions of normal and diseased human skin. The two proteins showed extensive codistribution. A continuous linear staining was found along the epidermal-dermal junction and around hair follicles, sebaceous gland acini and small capillaries. The same proteins also surrounded individual cells such as those found in vessels, hair erector muscles and subcutaneous tissue. Blister formation in bullous pemphigoi left type IV collagen and laminin on the floor of the blister, while the bullous pemphigoid antigen as detected by human autoantibodies was found on both sides of the blister. In solid basal cell carcinoma a strong staining was found around all tumour islands as well as focally within the cell clusters. This suggests that the tumour cells produce these basement membrane proteins but have lost, at least in part, control of polar deposition.

Skin fibroblasts were cultured from 13 patients with Osteogenesis imperfecta and collagen biosynthesis was investigated in vitro. In those patients characterised by only mild manifestations of the disease, the ratio of collagen types I and III was disturbed. By contrast, fibroblasts obtained from patients with Osteogenesis imperfecta of a more severe type synthesised collagen types I/III in a normal ratio.

Collagen was extracted by pepsin treatment from various tissues and skin fibroblasts of 23 patients belonging to different types of osteogenesis imperfecta (OI), and characterized by molecular sieve and ion exchange chromatography, gel electrophoresis, and amino acid analysis. We found an elevated collagen III/I ratio in the skin of one patient with OI type I but almost normal values in skin fibroblasts of two other patients of this OI type. Five patients with OI type II had a normal collagen III/I ratio in their skin and skin fibroblasts, but the degree of hydroxylation of lysine residues in collagen I and III from their skin, bone, calvarium, and noncalcified calvarial tissue was increased. Patients belonging to OI types II, III, and IV had also considerable amounts of collagen III in their long bones, while bone tissue from controls contained only type I collagen. The content of type V in calcified tissues was virtually the same in controls and patients.

We reviewed here a number of publications containing data on the quantitative aspects of collagen synthesis in vitro. In one section we discussed the factors which modulate the amount of collagen synthesized in various culture systems and in another section we presented experimental evidence for regulatory mechanisms operating in collagen synthesis on the transcriptional and/or translational levels. We believe that growing knowledge of the mechanisms controlling collagen synthesis will help us to understand and deal with fibrotic processes better.