Abstract
Background and purpose:Eucommia ulmoides polysaccharides (EUP) can regulate the immunity of macrophages, but the functional status of macrophages is related to osteoarthritis and synovial inflammation. The purpose of this study is to explore whether EUP has the effect of inhibiting osteoarthritis and its possible mechanism.Methods: MTT test was used to evaluate the appropriate concentration of EUP and real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to detect the effect of EUP on gene expression in RAW 264.7 cells. The osteoarthritis model was constructed by the anterior cruciate ligament transection (ACLT) in the rabbits. These rabbits were divided into three groups, sham operation group, OA group, and EUP group. The changes in articular cartilage were detected by gross observation and histological staining, and Micro-CT tested subchondral bone. Finally, the changes of macrophages in synovial tissue were studied by immunohistochemistry.Results: The results showed that EUP at the concentration of 50ug/mL and 100ug/mL were beneficial to the proliferation of macrophages. The qPCR results indicated that EUP inhibited the expression of inflammation-related genes IL-6, IL-18 and IL-1β, and promoted the expression of osteogenic and cartilage-related genes BMP-6, Arg-1 and transforming growth factor beta (TGF-β). The results of in vivo experiments suggested that the degree of destruction of articular cartilage in the EUP group was significantly reduced, and the Osteoarthritis Research Society International (OARSI) score was significantly reduced. Compared with the OA group, the subchondral cancellous bone density of the EUP group increased, the number and thickness of trabecular bone increased, and the separation of trabecular bone decreased. Synovial macrophage immunohistochemistry results manifested that EUP, on the one hand, reduced M1 polarized macrophages, on the other hand, accumulated M2 polarized macrophages.Conclusion: EUP can promote articular cartilage repair and subchondral bone reconstruction. The regulation of the polarization state of macrophages may be one of its mechanisms to delay the progression of osteoarthritis.
Highlights
Osteoarthritis is a degenerative joint disease, which is mainly manifested as progressive degeneration of articular cartilage, including narrowing of the joint space, changes in subchondral bone structure, osteophyte formation, synovitis etc., (Glyn-Jones et al, 2015)
Studies have shown that the cytokine IL-6, IL-1β and IL-18 can promote inflammation and apoptosis of chondrocytes, they inhibit the expression of aggrecan and stimulate the expression of MMPs, contribute to the pathogenesis of OA (Bao et al, 2020; Kapoor et al, 2011)
We found that EUP exhibited no obvious toxicity to cells at the concentrations of 50μg/ml and 100μg/ml, but favored cell proliferation. qPCR assay indicated that EUP significantly inhibited the expression of macrophage inflammation related genes IL-6, IL-18 and IL-1β and promoted the expression of osteogenesis and chondrogenesis related genes BMP-6, Arg-1 and TGF-β
Summary
Osteoarthritis is a degenerative joint disease, which is mainly manifested as progressive degeneration of articular cartilage, including narrowing of the joint space, changes in subchondral bone structure, osteophyte formation, synovitis etc., (Glyn-Jones et al, 2015). The normal synovial membrane is composed of the inner membrane layer and the subsynovial layer. The M1 type mainly promotes the occurrence of inflammation and can secrete inflammation-related cytokines such as IL-1β, IL-18 and IL-6, which in turn leads to cartilage degradation and the formation of osteophytes, while the M2 type is mainly responsible for anti-inflammatory and tissue repair (Zhang et al, 2020). Eucommia ulmoides polysaccharides (EUP) can regulate the immunity of macrophages, but the functional status of macrophages is related to osteoarthritis and synovial inflammation. The purpose of this study is to explore whether EUP has the effect of inhibiting osteoarthritis and its possible mechanism
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
