SVIBOR - Project code: 3-01-007

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Project code: 3-01-007


THE ROLE OF EXTRACELLULAR MATRIX IN CARTILAGE AND BONE MORPHOGENESIS


Main researcher: VUKIČEVIĆ, SLOBODAN (53835)



Assistants
Type of research: basic
Duration from: 01/01/90. to 12/31/95.

Papers on project (total): 32
Papers on project quoted in Current Contents: 25
Institution name: Medicinski fakultet, Zagreb (108)
Department/Institute: LABORATORY FOR CALCIFIED TISSUE BIOLOGY
Address: Šalata 11, 41000 Zagreb
City: 10000 - Zagreb, Croatia
Communication

Summary: Extracellular matrix, in particular basement membrane surrounding endothelial and epithelial cells in vivo has an important role in determining the cell growth and development. As osteoprogenitor cells and chondrocytes are in contact with basement membrane of blood vessels, which during osteogenesis invade cartilagenous long bone, it is possible that extracelullar matrix/basement membrane determine the growth and development of bones and cartilage. The aim of this project is to investigate the influence of extracelullar matrix and related growth factors on bone cells, chondrocytes and few skeleton-derived tumors. Experiments will be performed on the cellular, biochemical, molecular and morphological level, with the following specific methods and aims: - influence of basement membrane components (collagen type IV, laminin) on osteoblasts and chondrocytes in vitro and, their interaction with transforming growth factor -B (TGF-B) and bone morphogenetic proteins; - light and electron microscopy to determine morphological alterations of both cell types in contact with basement membrane; - gene expression of messenger RNA for basement membrane components by determining specific mRNA and proteins by specific antibodies; - synthesis of basement membrane components in vivo in experimental animals and man in healthy and diseased joints. The data should contribute to the better understanding of growth and development of bone and cartilage. Since, the regeneration of skeleton resembles its embrional development the understanding of osteo-chondrogenesis might help understanding the principles of biological repair of a healthy joint surface after traumatic, inflammatory and degenerative processess.

Keywords: extracellular matrix, growth and morphogenetic factors, bone, cartilage, differentiation, regeneration

Research goals: The aim of this project is to determine molecular events during osteo-chondrogenesis in experimental animals and men. The specific aims are as follows: 1. To investigate the influence of extracelullar matrix on human osteoblasts and chondrocytes. 2. To investigate the interactions between particular extracellular matrix components and growth factors and their effects on bone and cartilage cells. 3. To determine whether and where the extracellular matrix components are produced in vivo in healthy and altered bones and joints. 4. To determine the role of extracellular matrix components in inflammation. The scientific importants of this investigation is multiple. Understanding of molecular events during osteo-chondrogenesis will contribute to the better understanding of these processess, as well as factors influencing them directly. Irreversible damage of joint surfaces and neighbouring bones is a common health problem. Therefore, investigating the mechanisms of regeneration of bone and cartilage might lead to the discovery of new mechanisms of biological healing of the skeleton.


COOPERATION - PROJECTS



  1. Name of project: Bone morphogenetic proteins in cartilage and bone formation and regeneration
    Name of institution: Bone morphogenetic proteins in cartilage and bone formation and regeneration
    City: Bethesda, USA


COOPERATION - INSTITUTIONS


  1. Name of institution: Laboratory of Musculoskeletal Cell Biology, Dept.of Orthopaedic Surgery, J. Hopkins University, School of Medicine
    Type of institution: Economical/Production
    City: Baltimore, USA

  2. Name of institution: Laboratory of Develeopmental Biology, NIDR
    Type of institution: University/Faculty
    City: Bethesda, USA

  3. Name of institution: Center of Biologics Evaluation and Research, Food and Drug Administration
    Type of institution: University/Faculty
    City: Bethesda, USA

  4. Name of institution: Free University of Amsterdam, Academic Center for Dentistry, Faculty of Dentistry
    Type of institution: University/Faculty
    City: Amsterdam, Netherlands

  5. Name of institution: Childrens National Medical Center, Dept. of Otolaryngology, George Washington University, Washington D.C.
    Type of institution: International organization
    City: Washington, USA

  6. Name of institution: University of Ghent, Medical School, Dept. of Rheumatologz
    Type of institution: University/Faculty
    City: Ghent, Belgium

  7. Name of institution: Creative Biomolecules, Inc., Hopkinton,
    Type of institution: University/Faculty
    City: Boston, USA

  8. Name of institution: Endocrinology and Reproduction Branch, NICHD
    Type of institution: University/Faculty
    City: Bethesda, USA

  9. Name of institution: Laboratory of Chemoprevention, NCI
    Type of institution: University/Faculty
    City: Bethesda, USA

  10. Name of institution: Laboratory of Developmental Biology
    Type of institution: University/Faculty
    City: Bethesda, USA

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Last update: 10/10/95
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