Therapeutic Effect of Matrine on Collagen-Induced Arthritis Rats and Its Regulatory Effect on RANKL and OPG Expression.

Xin Li,Lin Mu,Lijie Zhang,Jing Ke,Baoyu Zhang,Yongsong Xu,Dong Zhao,Elizabeth Soares Fernandes

doi:10.1155/2021/4186102

Abstract

Objective To investigate the effect of matrine on rats with collagen-induced arthritis (CIA) and its regulatory effect on receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) expression. Methods Wistar rats (n = 6) and CIA rats (n = 30) were randomly divided into six groups: healthy, CIA control, low/medium/high matrine (25, 50, or 100 mg/kg, once per day for six weeks), and methotrexate (MTX) (2 mg/kg, once per week for six weeks). The degree of joint damage was evaluated by X-ray and HE staining. Bone marrow suppression was assessed by routine blood analysis. In addition, the levels of serum RANKL and OPG in the rats were measured by ELISA. Results The level of joint swelling and degree of joint damage assessed by ankle swelling measurements, AI score, X-ray, and HE staining were alleviated in the CIA rats treated with MTX or different doses of matrine. Furthermore, no obvious inhibitory effect was observed on the bone marrow of the CIA rats, regardless of the dose of matrine or treatment with 2 mg/kg MTX (P > 0.05). The levels of OPG in serum and the ratio of OPG/RANKL were higher, and RANKL expression was lower in the low/medium/high matrine group compared with that of the CIA control group. The serum levels of OPG and OPG/RANKL ratio increased with the matrine dose, while the opposite was observed for RANKL expression. Conclusion Matrine treatment was associated with a lower degree of bone destruction, increased OPG expression and OPG/RANKL ratio, and decreased RANKL expression in CIA rats. Thus, matrine may represent a novel drug candidate for the treatment of RA.

Highlights

Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical multijoint bone destruction, accompanied by a high disability and mortality rate
The RANKL/OPG ratio can determine the direction of bone change; a higher RANKL/OPG ratio indicates an increase in bone loss, while a lower ratio is associated with decreased bone loss [5]
We observed that the redness and swelling of the joints were more severe (P < 0:001), the arthritis index (AI) score was higher (P < 0:001), and the weight gain was lower in the collagen-induced arthritis (CIA) rats compared to the healthy rats (P < 0:05)

Summary

Introduction

Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical multijoint bone destruction, accompanied by a high disability and mortality rate. While decreased bone mass and bone destruction around the joints represent the main causes of disability in RA patients, no effective treatment is currently available to reverse or repair RA-induced cartilage and bone destruction. Increased secretion of receptor activator of nuclear factor-κB ligand (RANKL) is required for osteoclast differentiation [1]. The first is NF-κB receptor activator of nuclear factor-κB (RANK), which is mainly located on the cell membrane surface of osteoclast precursor cells. RANKL can bind to RANK to activate intracellular-related signaling pathways, which can promote osteoclastogenesis. The other receptor is osteoprotegerin (OPG), which is secreted by osteoblasts and exists in the extracellular matrix. OPG can compete with RANK to inhibit osteoclast differentiation [3, 4]. The RANKL/RANK/OPG system is important for regulating bone formation and bone destruction. The RANKL/OPG ratio can determine the direction of bone change; a higher RANKL/OPG ratio indicates an increase in bone loss, while a lower ratio is associated with decreased bone loss [5]

Methods

Results

Conclusion