Anterior Cruciate Ligament Transection–Induced Cellular and Extracellular Events in Menisci: Implications for Osteoarthritis

Abstract

Background: The meniscus plays an important role in knee joint diseases such as osteoarthritis (OA). Meniscal injuries can be accompanied by joint catabolic events initiated by inflammation, leading to articular cartilage destruction, but the cellular events responsible for intrinsic meniscal injury and the extracellular matrix changes necessary for meniscal degradation are not well known. Purpose: To explore the cellular and matrix-related changes of menisci based on a mouse OA model of anterior cruciate ligament transection (ACLT). Study Design: Controlled laboratory study. Methods: A mouse ACLT OA model was established by transection of anterior cruciate ligaments on the right knee joints of 8-week-old male (n = 34) and female (n = 34) C57 mice. The knee joints were collected at 1, 2, 4, and 8 weeks after ACLT surgery, and the meniscal changes were analyzed by radiography, histology, immunohistochemistry, immunoblot, and quantitative real-time polymerase chain reaction. Results: The deterioration of menisci was more extensive than that of articular cartilage and subchondral bone at 4 weeks after ACLT surgery. The rapid loss of collagen II and Sox9 in chondrocyte-like cells in the white-white zone of menisci was confirmed, and the activation of potential meniscus progenitor cells and chondroblasts was identified based on the increase of CD90, CD105, and Runx2. Further, the intrinsic inflammation in the bone marrow–like zone of menisci was activated by enhancement of dendritic cells (CD11c+), T cells (CD3+), and macrophages (F4/80+) with the increase of the inflammatory factors interleukin 1β and tumor necrosis factor α. Finally, the extracellular matrix events involving changes in chemokines, increases of matrix proteases (matrix metalloproteinases and ADAMTS5), and decreases of lysyl oxidase family were elucidated. Conclusion: ACLT-induced meniscal changes not only could explain the contribution of the meniscus to the progress of OA but also could provide a cue for initiation of preventive treatments in the early stages of OA. Clinical Relevance: This study provides support for better protection of menisci in ACL injury–induced conditions such as OA and indicates that menisci should be considered in the development of clinical pharmacological interventions.