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SCOPE OF RESEARCH

The research opportunities in the NIAMSD are as varied as the diseases it is attempting to learn about.

The field of orthopaedic research supported by the NIAMSD includes:

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basic and clinical studies of normal bone, bone growth, and bone metabolism; including investigation of cellular behavior;

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bone and joint diseases, injury, and repair;

therapies such as joint replacement, and bone cartilage transplantation to treat these diseases.

RESEARCH ADVANCES

Mr. Chairman, basic research is the lifeline of improved patient care. Each new bit of information, added to the previously existing scientific data base, contributes to clinical advances and the alleviation of human suffering.

The advances of the eighties have been truly remarkable. For example, adoption of cell and molecular biology and sophisticated analytic techniques has greatly advanced bone tissue research. Investigators have isolated substances found in bone matrix-- the extracellular material that becomes bone when hardened with mineral. These advances will have direct applications to patient care in the area of fracture repair and to ensure the fixation of artificial joints to the skeleton. Furthermore these advances will improve our understanding of congenital problems and bone tumors.

To understand this progress, some background information is essential. To begin with, most bone is not solid but composed of an outer layer of "cortical" bone surrounding "medullary" bone, a spongy network of bony tissue and hollow spaces. The laying down of new bone and resorption of old bone, in accordance with the metabolic needs and growth of the body is a continuous process known as "remodeling".

Long bones are composed of columns of cortical bone surrounding bone marrow. The ends of a typical long bone are thinner cortical plates covering spongy bone that is continuous with marrow, Osteocytes-- mature bone cells-- are distributed throughout spongy bone and along the concentric layers of bone tissue that make up the individual cylindrical structural units of cortical bone. Our new knowledge in these areas will be invaluable for the development of new clinical therapies for bone loss problems.

BONE FORMATION AND RESORPTION

The cells that form bone-- osteoblasts-- generate an extracellular matrix whose principal component is the protein colla

gen. in its many forms, collagen is the major constituent of skin, bone, nails, and the dentin of teeth. Type I collagen is the predominant form of collagen in bone matrix, but other collagens also are present. During wound healing, for example, quantities of type III collagen are synthesized. The remainder of bone matrix consist of noncollagenous proteins that play key roles in bone growth, maintenance and repair.

Several proteins purified from bone matrix are currently being studied for their ability to induce cartilage and bone growth. These advances will proivde the basis for treatment programs directed toward the stabilization and reversal of the bone loss associated with osteoporosis, a major health problem.

Complementing the function of osteoblasts are cells responsible for bone resorption, called osteoclasts. Recent research findings indicate that osteoclasts can release acids and enzymes that dissolve bone mineral and degrade the organic matrix. Our understanding in this area could help Poster unique therapies for reversing the problems of osteoarthritis, and slowly healing fractures.

THE COLLAGEN MOLECULE

while bone matrix is composed largely of type I collagen, cartilage matrix contains type II collagen secreted by chondrocytes. The matrix-generating cells secrete a precursor molecule, procollagen, which is cleaved to collagen extracellularly. Each collagen molecule consists of three polypeptide chains wound around each other to form a three-stranded rope. Bone collagen appears to be more crosslinked than skin collagen, involving both intramolecular and intermolecular crosslinks.

During the past decade, scientists have identified and cloned genes for a number of "decorator" collagens-- proteins involved in organizing the three-dimensional structure of collagen fibrils. This kind of genetic analysis is enabling scientists to identify markers for a number of collagen-defect diseases, such as bone disease (osteogenesis imperfecta) and recently a congenital form of osteoarthritis.

MATRIX PROTEINS

of the many important findings over the decade, few have aroused more excitement than the discovery of an increasing number of noncollagenous proteins in extracellular matrices. The isolation and characterization of these have been made possible by the development of such technologies as high-pressure liquid chromatography, nuclear magnetic resonance and gene cloning and sequencing techniques. Some matrix proteins are essential in linking cells to tissues. These "cell attachment proteins" include fibronectin, thrombospondin, osteopontin, and laminin. Hopefully, this data will enable scientists to construct biological artificial surfaces for treatment of arthritic problems which destroy joints.

Specific abnormalities in matrix proteins have been found in association with certain diseases-- for example, specific mutations in the type I collagen gene in cases of osteogenesis imperfecta.

Mr. Chairman, as we enter the nineties, there are many exciting opportunities for continued progress in understanding the diseases of the musculoskeletal system.

INTRAMURAL RESEARCH

The NIAMS intramural research program has a distinguished record of scientific achievement and represents a unique resource to the biomedical community. The orthopaedic laboratory has developed a research program conducting basic investigation at the cellular and molecular levels into the pathophysiology of diseases of the musculoskeletal system. The laboratory provides training for young orthopaedic surgeons and residents interested in basic research. The goal is to teach investigators research techniques and skills that they can use in basic studies of bone, cartilage, etc. We urge the committee to provide additional funding for this intramural program.

FUNDING REQUIREMENTS

We are fully aware of the difficult budgetary pressures facing the congress. However, we believe that adequate funding of the Nation's biomedical enterprise will result in decreased mortality, improved quality of life, and improved productivity through fewer days lost from work due to illness. We urge the committee to provide $251.7 million for the National Institute of Arthritis and Musculoskeletal and Skin Diseases. This is the funding level recommended by the Coalition of Voluntary and Professional Associations concerned with the programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. A copy of that recommendation is attached to this statement.

Moreover, Mr. Chairman, we support the recommendation of the Ad Hoc Group for Medical Research Funding that $9.7 billion is required for all of the programs at the National Institutes of Health.

We greatly appreciate this committee's past efforts to provide additional money to this Institute. with your continued support we can restore the millions of individuals afflicted with these diseases to independent status, and reduce the burden to society to care and pay for the medical services currently required.

on behalf of the over 14,000 fellows of the American Academy of Orthopaedic Surgeons and myself, thank you for giving us the opportunity to testify today.

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NIAMS research in progress is producing insight into skin mechanisms that have application in a number of skin diseases. And scientists are learning how to grow skin tissue, which could be beneficial to both skin disease and burn patients. Moreover, this Institute also deals with arthritis and musculoskeletal diseases, which are the leading cause of disability in the United States. A large number of Americans are affected by diseases that are of concern to NIAMS for example, 37 Million people of all ages are afflicted with arthritis, 27 Million have osteoporosis and related bone disorders and 60 Million people are treated annually for skin diseases. Skin diseases account for nearly six percent of all patient visits to physicians and are among the leading causes of time lost from work. The economic cost (including work loss) of arthritis, musculoskeletal and skin disease is substantially over $100 Billion per year. Thus, it is vital that continue the progress at NIAMS through increased funding. Unfortunately, NIAMS has been negatively impacted by this era of tight budgets because the institute

created in 1985. And in terms of dollars, the cost of doing biomedical research has doubled over the past decade; each dollar supports only half the research it did in 1979.

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Gratefully, due to the generosity of this Committee and its counterpart in the House,

the past few years funding for research project grants has increased. However, funding for research centers and other research and training programs has decreased. The availability of research training positions and research career awards is critical midlevel bridge between postgraduate education and investigative medicine. These research training positions and research career awards are essential if the nation expects its young people to commit to the rigorous demands of careers in biomedical research.

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Additionally, the funding of research centers

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