The Molecular Mechanism Investigation of HBP‐A Slows Down Meniscus Hypertrophy and Mineralisation by the Damage Mechanical Model

Abstract

HBP‐A is the main active component of a traditional Chinese medicine Huaizhen Yanggan Capsule, for the remarkable treatment of knee osteoarthritis (KOA). This study aimed to elucidate the ameliorative effect of HBP‐A on meniscus hypertrophy and mineralisation in KOA and the molecular mechanism of its action. An Hartley guinea pig model of KOA that underwent anterior cruciate ligament transection (ACLT) and a model of rat primary meniscus fibrochondrocytes (PMFs) were used to investigate the ameliorative effect of HBP‐A on meniscal hypertrophy and calcification and its signal transduction mechanism of action. The results show that Guinea pig's meniscus width, as well as the area of meniscus calcification and meniscus and articular cartilage injury score, were significantly reduced in the HBP‐A intervention group compared to the ACLT group. The expression levels of mtrix metalloproteinase 13 (MMP13), runt‐related transcription factor 2 (Runx2), Indian hedgehog (Ihh), alkaline phosphatase (ALP), and ankylosis homologue (ANKH) at the protein and gene level significantly decreased in the HBP‐A intervention group compared to the ACLT group. In vitro study, apoptosis, hypertrophy, and calcification of rat PMFs after 10% stretch force were significantly improved with HBP‐A intervention. Western blot and RT‐qPCR showed that hypertrophy, calcification, and p38 MAPK signalling pathway‐related markers of PMFs were incredibly depressed in the HBP‐A intervention group compared to the 10% stretch force group. In conclusion, HBP‐A can slow down meniscus hypertrophy and mineralisation induced by abnormal mechanical loading, and its mechanism of action may be through the p38‐MAPK signalling pathway.