Shari Ling, M.D.

Three informative presentations were delivered during the Cartilage Study Group
Background and Overview:
Replacement of diseased and damaged cartilage with autologous or engineered healthy chondrocytes is an area of intense investigation. The intent is to restore cartilage properties of load bearing, low friction and wear resistance. Repair of focal cartilage defects has been achieved with periosteol or perichondral tissue transplantation. Because the area of cartilage loss in OA can be quite extensive and because older chondrocytes are likely to be less metabolically active than younger chondrocytes, it remains doubtful that isolated cartilage transplantation approach will be practical in the treatment of established and advanced OA. However the presentations delivered focused on three unique approaches to cartilage engineering that will hopefully overcome these obstacles.

Molecular and Cellular Signaling in Cartilage Development
Rocky Tuan, Ph.D., coordinated by Dr. Rocky Tuan of the Cartilage Biology and Orthopedics Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland
The mechanisms responsible for normal cartilage growth and development must be delineated in order to mimic this complex process. Dr. Tuan reviewed the results of the basic studies on the mechanisms responsible for mesenchymal condensation and chondrogenic differation, and also the role of signal transduction proteins in these processes. The objective is to gain insights into the basis of normal and diseased cartilage phenotypes that will hopefully serve as a rational basis for the diagnosis and ultimately treatment of cartilage diseases, and as a predecessor for gene-based treatment for these diseases.

Articular Cartilage Tissue Engineering: Biomimetics and Biomechanics
Robert Sah, MD, ScD, University of California-San Diego
Dr. Sah addressed the topic of tissue engineering as a means of restoring, preserving or improving cartilage function. The involvement of living cells in the process of repair or restoration of cartilage distinguishes cartilage engineering from currently utilized prosthetic replacements. He reviewed the "faces" of cartilage during development, aging and disease (i.e. osteoarthritis) pathogenesis. Variations in collagen network structure appear to be an important determinant of its mechanical properties, and resident chondrocytes responsible for tissue metabolism thought to be responsible for its face properties. The biomimetic approach is based upon tissue engineering that will fabricate articular cartilage tissue capable of these structural and metabolic functions.

Cartilage Tissue Engineering: In Vitro generation and In Vivo Application
Lisa E. Freed, MD., Ph.D.Massachusetts Institute of Technology, Cambridge, MA
Dr. Freed presented her laboratorys development of engineered cartilage constructs to move forward our understanding of chondrogenesis, and to apply this bio-system towards scientific research and clinical use. Properties of engineered cartilage generated from bovine calf chondrocytes depend upon the scaffold material, scaffold 3-dimensional structure, and culture system used. Variation of this system, as well as adding growth factors and bioreactor vessels, can alter the structural, functional and molecular properties of engineered cartilage. The 3-D scaffold system was used to engineer cartilage from rabbit chondrocytes, and transplanted to result in orderly repair of large osteochondral defects. Beyond these achievements, engineered chondrocytes can be altered to over express one or more of these growth factors, into the defective cartilage site further facilitating repair.

References:

1. Delise AM, Fischer L, Tuan RS. Cellular interactions and signaling in cartilage development. Osteoarthr Cart 8: 809-34,2000.
2. Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage 10:432-63, 2002.
3. Sah RL: The biomechanical faces of articular cartilage. In: The Many Faces of Osteoarthritis, ed by KE Kuettner and VC Hascall, Raven Press, New York, 2002, (in press).
4. Pei M, Solchaga LA, Seidel J, et al., Bioreactors mediate the effectiveness of tissue engineering scaffolds, FASEB Journal 16: 1691-4, 2002.
5. Schaefer D, Martin I, Jundt G, et al., Tissue engineered composites for the repair of large osteochondral defects. Arthritis & Rheum 46:2524-34, 2002.
6. Tuan RS. Cellular signaling in developmental chondrogenesis: N-cadherin, Wnts, and BMP-2. J Bone Joint Surg (in press).
7. Tufan AC and Tuan RS. WNT regulation of limb mesenchymal chondrogenesis in vitro involves N-candherin mediated cell-cell adhesion. FASEB Journal 15:1436-8, 2001.

((top of page)) (next page)

All information contained within the Johns Hopkins Arthritis Center website is intended for educational purposes only. Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained within this site. Consumers should never disregard medical advice or delay in seeking it because of something they may have read on this website.