Cervus and cucumis peptides ameliorates bone erosion in experimental arthritis by inhibiting osteoclastogenesis

Abstract

ObjectiveRheumatoid arthritis is an autoimmune disease characterised by inflammation and bone loss, leading to joint destruction and deformity. The cervus and cucumis polypeptide (CCP) injection, one of the traditional Chinese medicine injections combined extracts from deer horn and sweet melon seeds, is widely used to treat arthritis and bone fracture in China. The present study investigated the therapeutic efficacy and mechanism of CCP on pathological immune cells and bone homoeostasis in rodent experimental arthritis.MethodsThe effects of CCP (4 mg/kg and 2 mg/kg) on clinical arthritis symptoms, bone erosion, proinflammatory cytokines and pathological immune cells induced by complete Freund’s adjuvant was evaluated in male Sprague-Dawley rats. The impacts of CCP (2 mg/kg) on joint erythema and swelling, production of pathogenic antibodies and the proportion of inflammatory cells were assessed in collagen-induced arthritis (CIA) in DBA/1J mice. Regulation of osteoclastogenesis by CCP was observed in the murine macrophage-like RAW264.7 cells treated with receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF).ResultsCCP administration significantly prevented disease progression in both adjuvant-induced arthritis (AIA) rats and CIA mice. The therapeutic benefits were accompanied by reduction of paw oedema, reversed bone destruction, decreased pathological changes and osteoclast numbers in joints in AIA rats, as well as attenuated clinical manifestation and autoantibodies production in CIA mice. Meanwhile, in vitro supplemented of CCP concentration dependently inhibited RANKL/M-CSF-induced osteoclast differentiation, without showing cytotoxicity in RAW264.7 cells. Further, the presence of CCP dampened the augmented downstream signalling transduction as well as activation of osteoclast-specific genes and transcription factors induced by RANKL/M-CSF in RAW264.7 cells.ConclusionOur study suggested that the therapeutic effects of CCP in experimental arthritis could be attributed to its intervention on RANKL-induced osteoclastogenesis signalling pathway in osteoclast precursor cells.

Evaluating the anti‐arthritic potential of walnut ( Juglans regia L.) in FCA induced Sprague Dawley rats

“…Moreover, it was revealed previously (Alves et al, 2016;Kamel et al, 2019) that RANKL pronounced expression in the positive control (FCA induced untreated rat) group whereas, treatment with MTX and bioactive components downregulated the RANKL gene expression, thus playing a protective role in bone erosion. The mRNA expression level of RANKL significantly increased in FCA induced positive control group whereas, the mRNA expression of OPG significantly reduced at the time of arthritis onset (Kishimoto et al, 2004;Lin et al, 2019), the same trend is observed in current research in which positive control group showed marked elevation in the expression level of RANKL, that is reverted back to its normal via walnut based treatments. The drug MTX is commonly used in the treatment of RA.…”

Cervus and cucumis peptides combined umbilical cord mesenchymal stem cells therapy for rheumatoid arthritis

“…[ 14 ] They inhibit the inflammatory response, reduce the content of tumor necrosis factor-alpha (TNF-alpha) in serum, [ 15 ] and assist macrophage-derived cytokines to play a role in tissue repair. [ 16 ] According to the pathogenesis of RA in traditional Chinese and western medicine, UC-MSCs are pre-stimulated by the polypeptide of LG to promote the superposition of kidney-nourishing, bone strengthening, blood-activating, and collateral-opening, and also reduce the release of pro-inflammatory factors. While stabilizing the internal environment, the biological characteristics of UC-MSCs migration, homing, regeneration, repair, and immune regulation can be enhanced, which also conform to the principle of specimen co-treatment in traditional Chinese medicine.…”

Mesenchymal Stem Cells‐Involved Strategies for Rheumatoid Arthritis Therapy

“…LG contains TGF‐β, which assists macrophage‐derived cytokines in tissue repair. [ 80 ] In addition, it inhibits inflammatory response and reduces TNF‐α levels in the serum. [ 80 , 81 ] In vitro, the secretion of anti‐inflammatory factors, such as HGF, PGE‐2, and TNF, was remarkably increased in the LG‐treated MSCs group.…”