Toddalolactone protects against osteoarthritis by ameliorating chondrocyte inflammation and suppressing osteoclastogenesis

Chinese Medicine

Haiming Lu¹  Weilin Sang¹  Jinzhong Ma¹  Cong Wang¹  Hongjie Chen¹  Libo Zhu¹  Xinmeng Jin²  Yiming Xu²  Yiming Zhong²  Tian Zhang³  Song Xue⁴ 

[1] Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Shanghai Bone Tumor Institution, Shanghai, China;Department of Orthopedics, The Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, China;Department of Rheumatology and Immunology, Arthritis Research Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, China;

关键词: Toddalolactone;    Cartilage;    Inflammation;    Osteoclastogenesis;    Osteoarthritis;   

DOI  :  10.1186/s13020-022-00576-w

来源: Springer

【 摘 要 】

BackgroundOsteoarthritis (OA) is widely recognized as the most common chronic joint disease accompanied by progressive cartilage and subchondral bone damage. Toddalolactone (TOD), a natural compound extracted from Toddalia asiatica (L.) Lam., has been widely used in the treatment of stroke, rheumatoid arthritis, and oedema. Nevertheless, what TOD acts as in the pathogenesis and progression of OA hasn’t been reported. In this investigation, we have aimed to determine how TOD affects OA in vitro and in vivo.MethodsLPS (10 µg/ml) and IL-1β (10 ng/ml) were employed to induce chondrocyte inflammation or RANKL to induce osteoclast differentiation in bone marrow derived macrophages (BMMs). The effects of TOD on chondrocyte inflammation and osteoclast differentiation were evaluated. Anterior cruciate ligament transection (ACLT) was performed to develop an OA animal model and study the effects of TOD.ResultsWe found that TOD inhibited the expression of inflammatory and catabolic mediators (IL-6, IL-8, TNF-α, MMP2, MMP9, and MMP13) in inflammatory chondrocytes in vitro. Furthermore, TOD was proven to inhibit RANKL-induced-osteoclastogenesis and inhibit the expression of osteoclast marker genes. Our data also confirmed that TOD suppressed the destruction of articular cartilage and osteoclastogenesis via inhibiting the activation of NF-κB and MAPK signalling pathways. In the ACLT mouse model, we found that TOD attenuated cartilage erosion and inhibited bone resorption.ConclusionsThese results showed that TOD can be adopted as a potential therapeutic agent for OA.

【 授权许可】

CC BY