Why Does the MCL Repair so Well After Injury, While the ACL and PCL do Not?
July 1, 2000 3 minutes read
Why Does the MCL Repair so Well After Injury, While the ACL and PCL do Not?
Abstract & Commentary
Synopsis: The ACL and PCL synthesize larger amounts of nitric oxide and synthesize less collagen and proteoglycans than the MCL.
Source: Cao M, et al. Does nitric oxide help explain the differential healing capacity of the anterior cruciate, posterior cruciate, and medial collateral ligaments? Am J Sports Med 2000;28:176-182.
This is a basic science study comparing the ability of the New Zealand white rabbit medial collateral ligament (MCL), anterior cruciate ligament (ACL), and posterior cruciate ligament (PCL) to produce nitric oxide (NO). Ligaments were placed into tissue or cell culture, and nitric oxide, collagen, and proteoglycan synthesis were compared. Cao and colleagues were not blinded to the ligament when recording the results.
The results indicate that the ACL and PCL spontaneously synthesize larger amounts of NO and synthesize less collagen and proteoglycans than the MCL. Furthermore, when stimulated with the inflammatory cytokine interleukin-1, ACL and PCL tissue produced much higher amounts of NO than did MCL tissue. When exogenous NO was applied to these tissues, it had a profound inhibitory effect on collagen synthesis by ACL and PCL tissues, while producing little effect on MCL collagen production. Lastly, endogenous NO inhibited collagen and proteoglycan production by ACL and PCL tissues, but had little effect on the MCL.
Comment by James R. Slauterbeck, MD
So, why do the ACL and PCL heal so poorly and the MCL so well? Many theories have been put forth that typically are divided between intrinsic and extrinsic explanations. The extrinsic explanations define that the environment immediately surrounding the ligament is different and is responsible for the variable reparative response. For example, the MCL is a capsular-type ligament with a better blood supply and outside the synovial fluid of the knee, which allows clot formation and a better healing environment. The other theory relies on the concept that the ACL, PCL, and MCL have different intrinsic repair potentials. That is, the cells within each ligament differ ultrastructually, morphologically, and physiologically in their response to tissue injury and repair.
This study looks at NO production differences between the ligaments. In a prior study, Cao et al found that NO in articular chondrocytes strongly inhibits collagen and proteoglycan synthesis. Additionally, it appears that NO inhibits healing by blocking matrix synthesis, prolonging the early stages of inflammation and blocking cell division. Therefore, a difference in the production or response to the NO between ligaments may provide an explanation for differential healing capabilities.
This paper identified a difference in the production of NO occurring between ACL, PCL, and MCL in tissue and cell culture. Both cell and tissue culture were used to verify that the NO synthesis was not a response to the preparation of the cell culture but actually a response of the cells to known NO-inducing and blocking agents. Both the cell and tissue culture responded appropriately, adding validity to their results. The cruciate ligaments appear to produce higher levels of NO de novo as well as in response to inflammatory cytokines, which would be released in response to injury.
Ultrastructural differences between similar tissues play an important role in the ability of that tissue to repair. Although not much is known about all the effects of NO on tissues, it looks promising that the production of NO alters tissue’s ability to respond to injury. Increased NO appears to inhibit collagen and proteoglycan synthesis, which would be essential to ligament healing. This paper adds to our knowledge base and proposes a new idea that NO production decreases the ability of ligament to heal. Therapeutically, a pharmacological agent that specifically inhibits NO production may help tissues heal faster and may someday help us to better repair injured ligaments.
Nitric oxide synthesis is proposed to inhibit healing by:
a. inhibiting collagen synthesis.
b. inhibiting proteoglycan synthesis.
c. prolonging the inflammatory phase of healing.
d. All of the above
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