Molecular biology of meniscus pathology: Lessons learned from translational studies and mouse models

Abstract

Injury to any individual structure in the knee interrupts the overall function of the joint and initiates a cascade of biological and biomechanical changes whose endpoint is often osteoarthritis (OA). The knee meniscus is an integral component of knee biomechanics and may also contribute to the biological homeostasis of the joint. Meniscus injury altering knee function is associated with a high risk of OA progression, and may also be involved in the initiation of OA. As the relationship between meniscus injury and OA is very complex; despite the availability of transcript level data on human meniscus injury and meniscus mediated OA, mechanistic studies are lacking, and available human data are difficult to validate in the absence of patient-matched noninjured control tissues. As similarities exist between human and mouse knee joint structure and function, investigators have begun to use cutting-edge genetic and genomic tools to examine the usefulness of the mouse as a model to study the intricate relationship between meniscus injury and OA. In this review, we use evidence from human meniscus research to identify critical barriers hampering our understanding of meniscus injury induced OA and discuss strategies to overcome these barriers, including those that can be examined in a mouse model of injury-mediated OA.

Keywords: genetics and genomics; meniscus; osteoarthritis; repair.

Fig. 1:. Simple diagram showing complex interaction between meniscus tear, degeneration and OA.

Meniscus tear and degeneration both often lead to OA over a course of years. New evidence suggests that OA also contributes to meniscus degeneration and likely increases the susceptibility to meniscus tear. Meniscus tear may precede meniscus degeneration or vice versa. Moreover, the presence of a number of confounding factors (listed in Table 1) further complicates this interaction.