Nitric Oxide and Tendon Healing . . . Relevance to Sports Medicine

Abstract & Commentary

Synopsis: Nitric oxide expression was increased following achilles tendon injuries and appeared to play a role in stimulating wound healing and remodeling.

Source: Lin JH, et al. Temporal expression of nitric oxide synthase isoforms in healing Achilles tendon. J Orthop Res. 2001;19(1):136-142.

Nitric oxide is a free radical that is involved with tissue healing. It is expressed after injury in many tissues including bone. Nitric oxide may be involved in tissue remodeling by stimulating inflammatory cell-programmed cell death (apoptosis), producing angiogenic and vasodilatory functions, and stimulating wound collagen production. This study was designed to evaluate the expression of nitric oxide production in surgically severed Achilles tendons in rats. Semiquantitative polymerase chain reaction (PCR) and Western Blotting were used to assess the gene expression and protein production. Tissue healing was recorded on days 4, 7, 14, and 21 after surgery to assess the inflammation, granulation, and remodeling phases of tissue remodeling.

Prior to injury, minimal if any nitric oxide synthase mRNA, protein, or enzyme production was present. After Achilles transection, nitric oxide mRNA, protein, and enzyme production all increased.

Comment by James R. Slauterbeck, MD

Ligament and tendon injuries occur frequently in the athletic population. Remodeling of injury ultimately determines safe and effective return of athletes to sport. Soft tissue remodeling is the process by which injury is repaired. Control of this process will alter the quality and quantity of repaired tissue. Understanding the remodeling process and the relationship to nitric oxide production following injury may help to develop methods that decrease healing time or increase quality of soft tissues after injury.

Many of the standard modalities including heat, ice, and electrical stimulation effectively decrease morbidity and facilitate early return after injury. However, if we want to better influence remodeling of the injury to favor repair, we must look more carefully at the molecular aspects of the process. Gene regulation of inflammatory mediators, matrix proteases, and collagen production could alter the timing and effectiveness of tissue repair.

Nitric oxide is a potent mediator of tissue repair that is involved with the remodeling process at the molecular level. Control of the nitric oxide production or delay of its degradation will likely increase the effects of its presence. Further study in this area may bring us closer to building stronger repaired tissues in a quicker fashion. This could decrease the time after injury and return athletes to sports sooner with stronger tissues and may add another tool to the sports medicine caregiver’s bag.