Cyclin B1 protects against meniscal extracellular matrix catabolism and degeneration via the NOD-like receptor pathway

Meniscus is vital for maintaining knee homeostasis and function, and its degeneration is linked to knee osteoarthritis (OA) progression. However, the pathological mechanism of meniscus degeneration remains elusive. This study aimed to identify the molecular biological role of Cyclin B1 (CCNB1) in meniscus degeneration. Meniscal transcriptome sequencing of OA/non-OA was performed, and CCNB1 expression was verified in human and experimental mouse meniscal samples. The mice were administered with lentiviruses with CCNB1 overexpression via intra-articular injection after anterior cruciate ligament transection (ACLT) surgery, and the extracellular matrix (ECM) components and catabolic indicators were detected by immunohistochemistry. The in vitro and transcriptome sequencing of overexpressed CCNB1 was used to explore the mechanism of CCNB1 in meniscal degeneration. NOD-like receptor pyrin domain containing three (NLRP3) and its inhibitor were tested in explants induced by interleukin 1β. CCNB1 was significantly downregulated in meniscus cells of patients with OA and ACLT mouse models. CCNB1 overexpression restored homeostasis in meniscus cells, leading to markedly attenuated ACLT-induced meniscal degeneration. Furthermore, target prediction using bioinformatics and transcriptome sequencing analysis identified NLRP3 as a target of CCNB1. The cellular and molecular analyses showed that the inhibitor of CCNB1 effectively protected meniscal explants from degeneration by inhibiting inflammatory processes. Conclusions: Our findings indicated an essential role of CCNB1 in the pathogenesis of meniscal degeneration. Targeting the CCNB1/NLRP3 axis may serve as a practical therapeutic strategy to delay meniscal degeneration.