Author:
Xu Yiming,Xue Song,Zhang Tian,Jin Xinmeng,Wang Cong,Lu Haiming,Zhong Yiming,Chen Hongjie,Zhu Libo,Ma Jinzhong,Sang Weilin
Abstract
Abstract
Background
Osteoarthritis (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.
Methods
LPS (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.
Results
We 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.
Conclusions
These results showed that TOD can be adopted as a potential therapeutic agent for OA.
Funder
National Natural Science Foundation of China
Shanghai Municipal Health and Family Planning Commission
Medical Engineering Cross Research Project of Shanghai Jiaotong University
Songjiang District Science and Technology Research project
Publisher
Springer Science and Business Media LLC
Subject
Complementary and alternative medicine,Pharmacology
Cited by
2 articles.
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