Several multidisciplinary research
programs are being vigorously pursued by the faculty and
staff of the center.
Bone Development and Repair
A re-evaluation of bone formation in
chick, mouse, and human embryos performed with molecular
probes and complex morphometric analysis has revealed
that several aspects of bone development have been
incorrectly assumed for many years. For example, the
details of first bone formation of the tibia follow many
of the same steps found in the cranium. Most
interestingly, it may be that the cartilage rod or model
which precedes bone formation serves as a guide for the
formation of the marrow cavity, not the bone itself.
Cartilage Biochemistry, Disease and Repair
Cartilage is a complex tissue which
serves several functions in the skeletal system. Most
notably, cartilage serves as a cushion on bone joint
surfaces. Studies on the molecules, proteoglycans and
collagens, which give articular cartilage its resiliency
and, thus, its cushioning ability and tensile strength
are being conducted in detail in normal and diseased
tissue. It may be that one cause for the breakdown of
cartilage in the elderly is due to inadequacies of the
proteoglycans made by cartilage cells. This possibility
is being explored by studies of the controlling elements
which regulate proteoglycan structure as well as by
studies which attempt to understand the interactions
between proteoglycans and collagens.
These research projects serves as the
basis for studies of cartilage repair in defects created
to explore the cellular and molecular events of the
repair process. Ironically, bioactive factors from adult
bone may prove to be the most potent enhancers of this
reparative process. Preliminary studies suggest that
considerable bone activity is involved in rheumatic
diseases such as osteoarthritis and rheumatoid
arthritis. Such information further reinforces the
center’s focus on both bone and cartilage. Ultimately,
it may be possible to use this focus on our accumulated
experience to successfully transplant entire cartilages,
bones, or complex joints into humans. Surely, our
efforts in the next decade will result in new insights
into both cartilage and bone repair and new treatment
protocols.
Fibroblasts
Fibroblasts are not the uniform and
physiologically inert population of cells that they were
once perceived to be. Instead, they constitute a
heterogeneous and physiologically active group of cells
that produce, organize, and remodel extracellular
matrix, and, simultaneously, these cells produce and
respond to various cytokines and growth factors.
Physiologic diversity within human dermal fibroblast
populations was identified by Harper and Grove who
demonstrated that fibroblasts from the papillary and
reticular layers of the same piece of skin exhibit
different proliferation kinetics, evidence that multiple
subpopulations of fibroblasts exist in skin. Recent
studies indicate that the DEJ-region of skin contains
multiple subsets of dermal fibroblasts. Current studies
are directed towards developing methods to separate
these subpopulations and to physiologically characterize
these cells. A combination of cell sorting and cloning
methods is being used to separate these cells.
Currently, potential subsets of cells are being
characterized for proliferation kinetics, cellular
morphology, and extracellular matrix production. These
studies will help to understand the complex
intercellular interactions that establish and maintain
skin homeostasis and interactions involved in wound
healing.
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