Abstract
Osteoarthritis (OA) is a common degenerative joint disease featuring the degeneration, destruction, and ossification of cartilage. Inflammation which may facilitate OA occurrence and development is considered as the main pathological factor. Betulin, a natural product extracted from birch bark, has been commonly used for inflammation treatment; however, its role in OA remains unclear. This study is aimed to explore whether betulin can suppress IL-1β–induced inflammation in chondrocytes and alleviate OA in vitro and in vivo. In in vitro studies, the generation of pro-inflammatory factors, such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2), and nitric oxide (NO), was assessed using the enzyme-linked immunosorbent assay (ELISA) and Griess reaction. As revealed by results, betulin inhibited the expression of pro-inflammatory mediators. In addition, the protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), matrix metalloproteinase (MMP-13), thrombospondin motifs 5 (ADAMTS5), Collagen II, and Aggrecan were quantified using Western blot analysis. We found that betulin could inhibit the generation of COX-2 and iNOS induced by IL-1β, indicating that betulin has anti-inflammatory effects in chondrocytes. Furthermore, betulin downregulates the expression of MMP-13 and ADAMTS-5 and upregulates the expression of Collagen II and Aggrecan, indicating that it can inhibit the degradation of the extracellular matrix. In mechanism, betulin activated the AKT/Nrf2 pathway and inhibited the phosphorylation of p65. In in vivo studies, administration of betulin in vivo could inhibit cartilage destruction and inflammatory progression. Therefore, these findings suggest that betulin may alleviate IL-1β–induced OA via the AKT/Nrf2/HO-1/NF-κB signal axis, and betulin may be a potential drug for the treatment of OA.
Highlights
Osteoarthritis (OA) is a long-lasting, chronic, and progressive joint disease characterized by the loss or destruction of joint function and morphological integrity
This study aims to explore whether betulin can reduce the inflammation level of OA by regulating the signal axis of protein kinase B (AKT)/nuclear factor–erythroid 2–related factor (Nrf2)/heme oxygenase-1 (HO-1)/nuclear transcription factor-κB (NF-κB), alleviating the progression of OA
The results showed that the protein levels of HO-1 and nuclear Nrf2 (Nu-Nrf2) increased significantly after betulin treatment compared to the control group (p < 0.01) and Nrf2 transfer to the nucleus (Figures 7A–D) (p < 0.01)
Summary
Osteoarthritis (OA) is a long-lasting, chronic, and progressive joint disease characterized by the loss or destruction of joint function and morphological integrity. It is mainly manifested as joint pain with serious impact on daily life (Kean et al, 2004). Previous studies have revealed that IL-1β can induce the activation of nuclear transcription factor B (NF-κB) and promote the secretion of pro-inflammatory mediators (Abramson et al, 2001; Vincenti and Brinckerhoff, 2002; Chabane et al, 2008; Zhang et al, 2018), resulting in the decomposition of the intra-articular matrix above the synthetic level (Dodge and Poole, 1989; Nummenmaa et al, 2015), and accelerating the deterioration of OA. Inhibiting the IL-1β–mediated inflammatory response is an effective therapeutic strategy to suppress the progression of OA
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
