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

Objective Rheumatoid 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 see...

Full description

Saved in:
Bibliographic Details
Main Authors: Ze-Min Lin, Yu-Ting Liu, Yan-Sheng Xu, Xiao-Qian Yang, Feng-Hua Zhu, Wei Tang, Shi-Jun He, Jian-Ping Zuo
Format: Article
Language:English
Published: BMJ Publishing Group 2019-12-01
Series:Lupus Science and Medicine
Online Access:https://lupus.bmj.com/content/6/1/e000331.full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850255856166240256
author Ze-Min Lin
Yu-Ting Liu
Yan-Sheng Xu
Xiao-Qian Yang
Feng-Hua Zhu
Wei Tang
Shi-Jun He
Jian-Ping Zuo
author_facet Ze-Min Lin
Yu-Ting Liu
Yan-Sheng Xu
Xiao-Qian Yang
Feng-Hua Zhu
Wei Tang
Shi-Jun He
Jian-Ping Zuo
author_sort Ze-Min Lin
collection DOAJ
description Objective Rheumatoid 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.Methods The 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).Results CCP 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.Conclusion Our 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.
format Article
id doaj-art-3e8ab4fa0da540518a8ff40aa0faeaa5
institution OA Journals
issn 2053-8790
language English
publishDate 2019-12-01
publisher BMJ Publishing Group
record_format Article
series Lupus Science and Medicine
spelling doaj-art-3e8ab4fa0da540518a8ff40aa0faeaa52025-08-20T01:56:46ZengBMJ Publishing GroupLupus Science and Medicine2053-87902019-12-016110.1136/lupus-2019-000331Cervus and cucumis peptides ameliorates bone erosion in experimental arthritis by inhibiting osteoclastogenesisZe-Min Lin0Yu-Ting Liu1Yan-Sheng Xu2Xiao-Qian Yang3Feng-Hua Zhu4Wei Tang5Shi-Jun He6Jian-Ping Zuo7Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai, ChinaLaboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai, ChinaLaboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLaboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai, ChinaLaboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai, ChinaLaboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai, ChinaLaboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai, ChinaLaboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai, ChinaObjective Rheumatoid 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.Methods The 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).Results CCP 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.Conclusion Our 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.https://lupus.bmj.com/content/6/1/e000331.full
spellingShingle Ze-Min Lin
Yu-Ting Liu
Yan-Sheng Xu
Xiao-Qian Yang
Feng-Hua Zhu
Wei Tang
Shi-Jun He
Jian-Ping Zuo
Cervus and cucumis peptides ameliorates bone erosion in experimental arthritis by inhibiting osteoclastogenesis
Lupus Science and Medicine
title Cervus and cucumis peptides ameliorates bone erosion in experimental arthritis by inhibiting osteoclastogenesis
title_full Cervus and cucumis peptides ameliorates bone erosion in experimental arthritis by inhibiting osteoclastogenesis
title_fullStr Cervus and cucumis peptides ameliorates bone erosion in experimental arthritis by inhibiting osteoclastogenesis
title_full_unstemmed Cervus and cucumis peptides ameliorates bone erosion in experimental arthritis by inhibiting osteoclastogenesis
title_short Cervus and cucumis peptides ameliorates bone erosion in experimental arthritis by inhibiting osteoclastogenesis
title_sort cervus and cucumis peptides ameliorates bone erosion in experimental arthritis by inhibiting osteoclastogenesis
url https://lupus.bmj.com/content/6/1/e000331.full
work_keys_str_mv AT zeminlin cervusandcucumispeptidesamelioratesboneerosioninexperimentalarthritisbyinhibitingosteoclastogenesis
AT yutingliu cervusandcucumispeptidesamelioratesboneerosioninexperimentalarthritisbyinhibitingosteoclastogenesis
AT yanshengxu cervusandcucumispeptidesamelioratesboneerosioninexperimentalarthritisbyinhibitingosteoclastogenesis
AT xiaoqianyang cervusandcucumispeptidesamelioratesboneerosioninexperimentalarthritisbyinhibitingosteoclastogenesis
AT fenghuazhu cervusandcucumispeptidesamelioratesboneerosioninexperimentalarthritisbyinhibitingosteoclastogenesis
AT weitang cervusandcucumispeptidesamelioratesboneerosioninexperimentalarthritisbyinhibitingosteoclastogenesis
AT shijunhe cervusandcucumispeptidesamelioratesboneerosioninexperimentalarthritisbyinhibitingosteoclastogenesis
AT jianpingzuo cervusandcucumispeptidesamelioratesboneerosioninexperimentalarthritisbyinhibitingosteoclastogenesis