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Does Nitric Oxide Help Explain the Differential Healing Capacity of the Anterior Cruciate, Posterior Cruciate, and Medial Collateral Ligaments?

Min Cao, MD, Maja Stefanovic-Racic, MD, PhD, Helga I. Georgescu, Freddie H. Fu, MD and Christopher H. Evans, PhD, DSc

Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Presented at the 24th annual meeting of the AOSSM, Vancouver, British Columbia, Canada, July 1998.

Address correspondence and reprint requests to Christopher H. Evans, PhD, DSc, Center for Molecular Orthopaedics, Harvard Medical School, 221 Longwood Avenue, BL-152, Boston, MA 02115

This study compared the ability of rabbit medial collateral ligament, posterior cruciate ligament, and anterior cruciate ligament tissue to synthesize nitric oxide, and determined its effects on matrix synthesis, an important component of ligament repair. It is not known whether ligament cells can produce nitric oxide and, if so, whether it influences healing of ligament injuries. The anterior cruciate and posterior cruciate ligament tissue produced large amounts of nitric oxide in response to the inflammatory cytokine interleukin-1. Medial collateral ligament, in contrast, produced only modest amounts of nitric oxide. Furthermore, anterior cruciate ligament and, to some degree, posterior cruciate ligament synthesized nitric oxide spontaneously in culture, whereas medial collateral ligament never did so. When nitric oxide was supplied to these tissues, it strongly inhibited collagen synthesis by the two cruciate ligaments, but had little effect on collagen synthesis by the medial collateral ligament. Endogenously synthesized nitric oxide was also able to inhibit collagen synthesis as well as proteoglycan synthesis by the two cruciate ligaments, but had little effect on matrix synthesis by the medial collateral ligament. We propose a novel hypothesis, based on nitric oxide production and matrix synthesis, that may help explain why the two cruciate ligaments have such limited healing capacity compared with the medial collateral ligament.