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ZhiJingSan Inhibits Osteoclastogenesis via Regulating RANKL/NF-κB Signaling Pathway and Ameliorates Bone Erosion in
Yuanyuan Ling1, Jie Yang1, Di Hua1
1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Abstract:
Bone erosion is the most evident pathological condition of rheumatoid arthritis (RA), which is the main cause of joint deformities and disability in RA patients. At present, the conventional RA drugs have not achieved satisfactory effect in improving bone erosion. ZhiJingSan (ZJS), which is a traditional Chinese prescription composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch, scolopendridae) and scorpion (dried body of Buthus martensii Karsch, Buthus), exhibits anti-rheumatism, analgesic and joint deformities improvement effects. This study aimed to assess the therapeutic effect of ZJS on RA bone erosion and to elucidate the underlying mechanism. The effect of ZJS on RA bone erosion was investigated in a murine model of bovine collagen-induced arthritis (CIA), and the underlying mechanism was investigated in vitro in an osteoclast differentiation cell model. Administration of ZJS delayed the onset of arthritis, alleviated joint inflammation, and attenuated bone erosion in the CIA mice. Meanwhile, ZJS decreased the serum levels of TNF-α, IL-6, and anti-bovine collagen II-specific antibodies. Furthermore, ZJS treatment reduced the number of osteoclasts and the expression of cathepsin K in the ankle joints of CIA mice. ZJS also inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation and the expression of MMP9 and cathepsin K in vitro. Mechanistically, ZJS blocked RANKL-induced p65 phosphorylation, nucleation, and inhibited the expression of downstream NFATc1 and c-Fos in bone marrow-derived macrophages (BMMs). Taken together, ZJS exerts a therapeutic effect on bone erosion in CIA mice by inhibiting RANKL/NF-κB-mediated osteoclast differentiation, which suggested that ZJS is a promising prescription for treating RA bone erosion.
Insights
ZhiJingSan (ZJS) effectively treats rheumatoid arthritis (RA) bone erosion by inhibiting osteoclast differentiation via the RANKL/NF-κB pathway. This traditional Chinese medicine shows promise for managing RA joint damage.
Area of Science:
- Rheumatology
- Immunology
- Pharmacology
Background:
- Rheumatoid arthritis (RA) is characterized by bone erosion, leading to joint deformities and disability.
- Current RA treatments often fail to adequately address bone erosion.
- ZhiJingSan (ZJS), a traditional Chinese prescription, demonstrates potential anti-rheumatism and analgesic properties.
Purpose of the Study:
- To evaluate the therapeutic efficacy of ZJS on bone erosion in a murine model of rheumatoid arthritis.
- To elucidate the underlying molecular mechanisms by which ZJS exerts its therapeutic effects.
Main Methods:
- A collagen-induced arthritis (CIA) mouse model was used to assess ZJS's effect on RA bone erosion.
- In vitro studies utilized an osteoclast differentiation model to investigate ZJS's mechanism of action.
- Key molecular pathways, including RANKL/NF-κB signaling, were analyzed.
Main Results:
- ZJS administration delayed arthritis onset, reduced joint inflammation, and attenuated bone erosion in CIA mice.
- ZJS decreased serum levels of TNF-α, IL-6, and anti-collagen II antibodies.
- ZJS inhibited osteoclast differentiation and expression of cathepsin K and MMP9 by blocking RANKL-induced NF-κB signaling in vitro.
Conclusions:
- ZJS demonstrates significant therapeutic effects against RA bone erosion.
- The mechanism involves the inhibition of RANKL/NF-κB-mediated osteoclast differentiation.
- ZJS represents a promising therapeutic candidate for treating rheumatoid arthritis-associated bone erosion.
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