S zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGF eminars in Arthritis and Rheumatism zyxwvutsrqponmlkjihgfedcb VOL. XIII, NO. 1 AUGUST 1983 Collagen: Structure, Function, and Metabolism in Normal and Fibrotic Tissues By Marcel E. Nimni zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM C OLLAGEN is the single most abundant animal protein in mammals accounting for about 30% of all proteins. The collagen molecules, after being secreted by the cells, assemble into characteristic fibers responsible for the functional integrity of tissues such as bone, cartilage, skin, and tendon (Fig. 1). They contribute a structural framework to other tissues such as blood vessels and most organs. Crosslinks between adjacent mol- ecules are a prerequisite for the collagen fibers to withstand the physical stresses to which they are exposed. Significant progress has been made towards understanding the functional groups on the molecules that are involved in the formation of such crosslinks, their nature, and location. A vari- ety of human conditions, normal and pathologic, involve the ability of tissues to repair and regener- ate their collagenous framework. Some of these conditions are characterized by excessive deposi- tion of collagen (e.g., cirrhosis, scleroderma, keloid, pulmonary fibrosis, diabetes, etc.). After trauma or surgery, abnormal deposition of collagen may impair function (adhesions following repair of long tendons, scar formation during healing, etc.). In addition, many disabling conditions result from changes in the nature and organization of collagen (heart-valve lesions, osteoarthritis, rheumatoid arthritis, and congenital collagen diseases such as Marfan’s and Ehlers-Danlos syndromes, osteogen- esis imperfecta, etc.). In human tissues there are five different col- lagen types that have been well characterized. Many others are currently being studied. We know that collagen molecules in cartilage differ from those in cornea, tendon, bone matrix, der- mis, the parenchyma of organs, periodontal liga- ments, and many other locations within the orga- nism. Why is cornea transparent, tendon tough, inelastic and able to sustain significant stresses, and cartilage resilient and viscoelastic? What kind of uniqueness is there in the chemical structure of collagen that enables these tissues to perform such diverse biologic functions? What regulates fiber diameter, orientation, concentra- tion of fibers in a particular volume of tissue, and packing of the fibers into larger bundles? How can we understand the problem of aging of connective tissues and changes related to pathol- ogy? It now seems as if mesenchymal cells that have acquired the ability to make a particular type of collagen can be influenced by environ- mental factors to change the rate and nature of the collagen molecules that they synthesize, and that in some instances these changes are revers- ible. This review will address itself to the various fundamental steps of the anabolism and catabo- lism of collagen as well as to the unique types of collagen present in skin, tendon, bone, blood vessels, cartilage and basement membranes and will focus on diseases associated with excessive accumulation of collagen, which leads to various forms of fibrosis. THE COLLAGEN MOLECULE The arrangement of amino acids in the col- lagen molecule is shown schematically in Fig. 2. zyxwvutsrq From the Departments of Biochemistry. M edicine and Orthopaedics, University of Southern California and Ortho- paedic Hospital, Los Angeles. CA. Supported in part by NIH grams AMlO35X. AMl6404. and AG02.577, as well as funds from the O rthopaedic Hospital. Address reprint requests to M arcel E. Nimni. Ph.D., Professor of Biochemistry, Medicine & Orthopedics. Bone & Connective Tissue Research Laboratory, P.O. Box 60132 Terminal Annex, Los Angeles, CA 90060. 0 1983 by Grune & Stratton, Inc. 0049-0172/83/1301-0001$5.00/0 Seminars in Artbntis and Rheumatism. Vol. 13, No. 1 (August), 1983 1