THE ROLE OF EXTRACELLULAR MATRIX IN CARTILAGE AND BONE MORPHOGENESIS
Main researcher
: VUKIČEVIĆ, SLOBODAN (53835) Assistants
STAVLJENIĆ, ANA (44681)
VINTER, IVAN (52404)
MARUŠIĆ, ANA (136152)
KUŠEC, VESNA (93843)
ČEŠNJAJ, MIRJANA (136141)
KRAJINA, MIRNA (149156)
MARTINOVIĆ, IGOR (106744)
MIHALJEVIĆ, TOMISLAV (179040)
ŽIC, RADO (190174)
MARTINOVIĆ-GRGAČIĆ, SNJEŽANA (900564)
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.
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
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
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
Name of institution
: Laboratory of Develeopmental Biology, NIDR Type of institution: University/Faculty City: Bethesda, USA
Name of institution
: Center of Biologics Evaluation and
Research, Food and Drug Administration Type of institution: University/Faculty City: Bethesda, USA
Name of institution
: Free University of Amsterdam, Academic
Center for Dentistry, Faculty of Dentistry Type of institution: University/Faculty City: Amsterdam, Netherlands
Name of institution
: Childrens National Medical Center, Dept. of
Otolaryngology, George Washington University, Washington D.C. Type of institution: International organization City: Washington, USA
Name of institution
: University of Ghent, Medical School, Dept.
of Rheumatologz Type of institution: University/Faculty City: Ghent, Belgium
Name of institution
: Creative Biomolecules, Inc., Hopkinton, Type of institution: University/Faculty City: Boston, USA
Name of institution
: Endocrinology and Reproduction Branch,
NICHD Type of institution: University/Faculty City: Bethesda, USA
Name of institution
: Laboratory of Chemoprevention, NCI Type of institution: University/Faculty City: Bethesda, USA