Chondromodulin-I derived from the inner meniscus prevents endothelial cell proliferation

The meniscus is a fibrocartilaginous tissue that plays an important role in controlling complex biomechanics of the knee. A perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Anti‐angiogenic molecules, such as chondromodulin‐I (ChM‐I) and endostatin, have pivotal roles in preserving the avascularity of cartilage. However, the anti‐angiogenic role of ChM‐I is unclear in the meniscus. We hypothesized that the inner meniscus might maintain its avascular feature by expressing ChM‐I. Immunohistochemical analyses revealed that ChM‐I was mainly detected in the inner and superficial zones of the meniscus. On the other hand, endostatin distribution was similar between the inner and outer meniscus. In Western blot, ChM‐I was detected only in the inner meniscus, whereas endostatin was equally observed in both inner and outer menisci. In addition, ChM‐I concentration of the inner meniscus‐derived conditioned medium was higher than that of the outer meniscus‐derived medium. ChM‐I removal from the inner meniscus‐derived medium and functional blocking of ChM‐I significantly increased endothelial cell proliferation. In this study, we demonstrated that the inner meniscus contained larger amounts of ChM‐I, and that the inner meniscus‐derived ChM‐I inhibited endothelial cell proliferation. Our results suggest that ChM‐I may be a key anti‐angiogenic factor for maintaining the avascularity of the inner meniscus. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 538–543, 2013