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The Effect of Cytokines on the Proliferation and Migration of Bovine Meniscal Cells

Madhu M. Bhargava, PhD, Erik T. Attia, George A. C. Murrell, MD, PhD, Martin M. Dolan, Russell F. Warren, MD and Jo A. Hannafin, MD, PhD

Laboratory for Soft Tissue Research, Hospital for Special Surgery, affiliated with New York Hospital, Cornell University Medical Center, New York, New York

Presented at the annual meeting of the Orthopaedic Research Society, San Francisco, California, February 1997.

Address correspondence and reprint requests to Jo A. Hannafin, MD, PhD, Hospital for Special Surgery, 525 East 70th Street, New York, NY 10021

We determined the effect of cytokines on the proliferation and migration of cells isolated from the inner-third (white-white), middle-third (red-white), and outer-third (red-red) regions of bovine meniscus. Cells from the outer, or peripheral, region of the meniscus exhibited higher DNA synthesis in the presence of 10% serum compared with cells from the inner or central regions. Recombinant human platelet-derived growth factor-AB, hepatocyte growth factor/scatter factor, and bone morphogenic protein-2 stimulated DNA synthesis of all meniscal cells in a dose-dependent manner, with a two- to threefold maximal stimulation at 10 ng/ml. Cell migration was also stimulated by addition of cytokines. Platelet-derived growth factor and hepatocyte growth factor caused an increase in the migration of cells derived from all three zones, while interleukin-1 selectively stimulated the migration of outer-zone meniscal cells. Epidermal growth factor was much less effective and stimulated the migration of cells in the inner and outer zones by 40% to 50%, while bone morphogenic protein-2 and insulin-like growth factor-1 stimulated the migration of meniscal cells from the middle zone by 40% to 50%. The identification of cytokines that stimulate both the growth and migration of meniscal cells may provide new tools for modulation of meniscal healing.

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