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.

 

Cancer Bone Metastasis

Bone is a preferred organ for cancer dissemination (metastasis) from various tumor malignancies, which most of the time is a terminal condition. At the target organ, the local microenvironment and cell-to-cell interactions between invading and resident cells constitute critical components during the establishment and progression of bone metastasis. Our research focus is to understand the mechanism(s) behind the establishment of bone metastasis based on a novel hypothesis suggesting that perivascular Mesenchymal Stem Cells (pMSCs) in the bone marrow control cancer cell invasion to the bone. This new hypothesis provides clinically relevant information for therapeutic strategies that innovatively aim at reducing bone metastasis by closing the gate through which the metastatic cancer cell transit into the bone, thus, providing a paradigm for improving the devastating outcomes of bone metastasis.

 

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.
 

Engineered Cartilage Evaluation

Please see the Case Center for Multimodal Evaluation of Engineered Cartilage (an NIBIB-funded P41 BTRC) website for more information on this research program.