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The Journal of Bone and Joint Surgery (American) 84:793-799 (2002)
© 2002 The Journal of Bone and Joint Surgery, Inc.

Scientific Article

Brief Exposure to High-Dose Transforming Growth Factor-ß1 Enhances Periosteal Chondrogenesis in Vitro

A Preliminary Report

Yasushi Miura, MD, Javad Parvizi, MD, James S. Fitzsimmons, BSc and Shawn W. O'Driscoll, PhD, MD

Investigation performed at The Cartilage and Connective Tissue Research Laboratory, Mayo Clinic, Rochester, Minnesota

Yasushi Miura, MD
Department of Orthopaedic Surgery, Nagoya University School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466, Japan

Javad Parvizi, MD
James S. Fitzsimmons, BSc
Shawn W. O'Driscoll, PhD, MD
The Cartilage and Connective Tissue Research Laboratory, Room 3-31, Medical Science Building, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905. E-mail address for S.W. O'Driscoll: odriscoll.shawn{at}mayo.edu

In support of their research or preparation of this manuscript, one or more of the authors received grants or outside funding from the Medical Research Council of Canada (MA 10879), the Arthritis Society of Canada (90053), and the Canadian Orthopaedic Research and Education Foundation. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: Articular cartilage has limited potential for repair. There have been various attempts aimed at improving the repair process in articular cartilage. Transforming growth factor-ß1 (TGF-ß1) has a stimulatory effect on chondrogenesis in periosteal explants. The purpose of the present study was to determine the effect of brief exposures (i.e., thirty and sixty minutes) of high concentrations of TGF-ß1 on periosteal chondrogenesis.

Methods: Five hundred and seventy-three periosteal explants were harvested from forty-six two-month-old male New Zealand White rabbits. Explants were exposed to 50 or 100 ng/mL of TGF-ß1 for thirty or sixty minutes. The amount of cartilage formed was then determined with use of a standardized six-week agarose culture assay.

Results: There was a significant increase in the amount of cartilage formation (p < 0.01), Type-II collagen content (p < 0.05), and sulfate incorporation (p < 0.0001) in explants treated with TGF-ß1. Maximal stimulation occurred following exposure to 100 ng/mL of TGF-ß1 for thirty minutes. There was also an increase in chondrocyte proliferation as measured by [ 3 H-] thymidine incorporation on day 5 of culture (p < 0.049).

Conclusions: The findings of this study indicate that exposure to TGF-ß1 has a stimulatory effect on periosteal chondrogenesis. This stimulatory effect is observed even with a very brief exposure time of thirty minutes.

Clinical Relevance: A possible clinical application of these findings is exposure of periosteal grafts that are currently utilized clinically to resurface articular defects to TGF-ß1 during the short time between graft procurement and implantation into the joint. This may obviate the need for intra-articular administration of TGF-ß1 and may enhance the ultimate graft incorporation and quality of cartilage repair.


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