Bone: Formation by Autoinduction

Abstract

Marshall R. Urist (Fig 1) was born on June 11, 1914 in Chicago, IL, where he spent his early life. After obtaining his bachelor’s degree from the University of Michigan, he returned to Chicago where he received a master’s degree from the University of Chicago. He then went to Baltimore where he earned his medical degree from the Johns Hopkins medical school in 1941. After a surgical internship at the Johns Hopkins Hospital, Urist began an orthopaedic residency in Baltimore. This was interrupted by military service (1943–1946) beginning in the California-Arizona Maneuver Area, extending through service in hospitals in Germany, and ending in the Surgeons General’s Office as an Orthopaedic Consultant.Fig 1.: Marshall R. Urist, MD, PhD.After discharge from the army, Urist finished his orthopaedic training at the Massachusetts General Hospital and the Boston Children’s Hospital. In 1947, Urist returned to the University of Chicago as an intructor in the Department of Physiology. It was here that he began his association with Franklin C. McLean, a pioneer in the study of the physiology of bone, which resulted in their authorshop of a monograph on bone physiology. 1 The direction of Urist’s career was determined by his association with McLean, and he never wavered in his zeal to investigate problems posed by bone physiology. Urist moved to Los Angeles, CA, where he opened a laboratory at the University of California Los Angeles. He was one of the early members of the surgical faculty and had an active clinical practice. As a clinical surgeon, Urist made substantial contributions to the development of total hip replacement using metal acetabular and femoral components. His contribution to the teaching program led to his appointment as a professor of orthopaedic surgery in 1969. In addition to participating in many national and international orthopaedic societies and representing his specialty as a consultant on many important national committees, Urist found the time to work on the editorial board of the journal, Clinical Orthopaedics. In 1966, he became editor of this journal and broadened its scope to include papers reflecting the research interests of the orthopaedic community. This led to a change of names, Clinical Orthopaedics became Clinical Orthopaedics and Related Research. To many, Urist’s editorship of the journal was one of his greatest achievements. His 27 years of leadership established the journal as a major source of clinical/material and research for practitioners and students. While juggling all of these balls, Urist continued to patiently and thoroughly study bone physiology in his laboratory. The work from his laboratory was awarded two Kappa Delta Awards (1950, 1981). The focus of his research for the past 50 years has been on bone induction. Therefore, it is appropriate that this symposium begins with one of his papers as the classic article. BONE: FORMATION BY AUTOINDUCTION Marshall R. Urist Abstract. Wandering histiocytes, foreign body giant cells, and inflammatory connective-tissue cells are stimulated by degradation products of dead matrix to grow in and repopulate the area of an implant of decalcified bone. Histiocytes are more numerous than any other cell form and may transfer collagenolytic activity to the substrate to cause dissolution of the matrix. The process is followed immediately by new-bone formation by autoinduction in which both the inductor cells and the induced cells are derived from ingrowing cells of the host bed. The inductor cell is a descendant of a wandering histiocyte; the induced cell is a fixed histiocyte or perivascular young connective-tissue cell. Differentiation of the osteoprogenitor cell is elicited by local alterations in cell metabolic cycles that are as yet uncharacterized. New evidence in favor of the theory of induction can be gathered from the process of bone formation in the interior of an implant of acellular, devitalized, decalcified, bone matrix. Differing from previous demonstrations of induction systems, which produce scanty deposits and less than 30-percent positive results, decalcified bone yields new bone in an amount proportional to the volume of the implant; the percentage of positive experimental results is as high as over 90 percent. The results of some 70 experiments on approximately 300 animals are summarized below to introduce a hypothesis of postfetal osteogenesis by autoinduction. Long bones, excised from adult rabbits and other laboratory animals, were cut in lengths of 1 to 2 cm and decalcified, unfixed, in 0.6 N HCl. Samples of human cortical bone obtained from accident cases, excised under aseptic conditions at autopsy, were lyophilized, and decalcified similarly in sterile solutions of 0.6 N HCl for a period of 5 days. The acid was removed by prolonged washing in sterile 0.15 M NaCl. The chemical composition of HCl-decalcified bone matrix, in millimoles per liter, per kilogram, was total Ca, 4.4±2.6; total P, 17.5±3.0; Na, 16.3±1.8