Authors: Lovorka Grgurevic Marko Pecina Slobodan Vukicevic
Publish Date: 2017/02/11
Volume: 41, Issue: 5, Pages: 1065-1069
Abstract
Over the last 40 years International Orthopaedics has published a series of articles on bone morphogenetic proteins BMPs covering topics from basic research to clinical applications This includes also work submitted from the Laboratory for Mineralized Tissues of the School of Medicine University of Zagreb Accordingly we felt obliged to give a short summary of Dr Urist’s life and work as our gratitude to his discovery that demineralized bone matrix DBM activity induces bone when implanted ectopically into the muscle or under the skin due to bone inducing proteins named BMPsDr Marshall R Urist was born in Chicago on June 11 1914 and grew up on a small farm in South Haven Michigan He received his undergraduate degree in chemistry from the University of Michigan and after earning a master’s degree at the University of Chicago entered the Johns Hopkins University School of Medicine receiving his medical degree in 1941 He completed his surgical residency at Johns Hopkins and at Massachusetts General Hospital MGH Urist joined the war in 1943 as Chief of Orthopaedics in the 22nd General Hospital Division in England and the 97th General Hospital Division in Germany After resigning from the military he became a senior resident at MGH and completed his training with a fellowship in orthopaedic surgery at Children’s Hospital in Boston where he worked on the management of poliomyelitis In 1947 he moved to Chicago to resume his collaboration with Franklin McLean at the Department of Physiology and Research His experiments focused on osteoporosis and hormone regulation of bone homeostasis 2 In 1948 he joined the faculty of the new School of Medicine at the University of California at Los Angeles as an Assistant Professor of Surgery He was promoted to Associate Professor in 1954 and to Professor of Surgery Orthopaedics in 1969 He died at his home on February 4 2001 in Los Angeles 4Dr Urist’s areas of interest include bone and joint biology bone morphogenetic proteins calcium metabolism bone grafts oestrogens and bone metabolism He contributed to the discipline of orthopaedic surgery in many ways but the main contribution was his interest in basic research 23 With grants from a private foundation he set up the Bone Research Laboratory in WilshireBone regeneration was the main concern of Dr Urist since his graduation when he read the book by Leriche and Policard where authors mentioned “the juice of stonemaking” which generates bone in muscle 2 The phenomenon of heterotopic bone formation was best described in experiments performed by Charles Huggins 1929–1931 on the uroepithelial tissue in dogs Huggins was awarded the 1966 Nobel Prize for Physiology or Medicine for his discovery that hormones could be used to control the spread of some cancers This was the first discovery that cancer could be controlled by chemicals 14 15In 1965 Dr Urist showed that new bone formation could be induced by DBM implanted under the skin or into the muscle of animals 29 With these studies Dr Urist pioneered the concept of substance naturally present in bone responsible for the regeneration and bone repair activity He called this substance the bone inductive principle BMP bone morphogenetic protein introducing the new term to describe the nature of this bone inductive factor and initiated a search for these molecules 30 He spent the next three decades isolating and purifying BMP molecules Throughout the 1970s preclinical research in Dr Urist’s laboratory demonstrated the involvement of BMP in the bone formation cascade of mitosis chemotaxis differentiation callus and bone formation endochondral and intramembranous The advances in molecular biology in the 1980s and early 1990s allowed the sequencing and cloning of BMPs Cloned for the first time in 1988 by a research team at the Genetics Institute led by Dr John Wozney BMP proved to be a member of the TGFbeta superfamily of cytokines 40 The first publications on the clinical use of BMP in nonunions and segmental bone defects began in the late 1980s by Johnson et al 16 in tibial defects Dr Urist’s work resulted in the publication of over 400 papers and the presentations of more than 200 lectures throughout the world Availability of rhBMPs permitted the large scale evaluation of their efficacy and safety in a large number of animal models thus allowing for optimization of both carrier and dose of BMPs for clinical use 6 8 9 10 11 13 17 19 21 22 24 27 38
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