QingreHuoxue decoction protects joint and toe bone morphology and structure in rats with active RA through bidirectional regulation of bone metabolism

QingreHuoxue decoction (QRHX) is a well-known traditional Chinese medicine formula for treating rheumatoid arthritis (RA). It is not known how QRHX is involved in bone metabolism regulation and thereby alleviatesbone injury caused by arthritis. In this study, we used collagen-induced arthritis (CIA)...

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Main Authors: Hui Yang, Zhenyu Wu, Xun Gong, Bo Li, Guangjun Wu, Quan Jiang
Format: Article
Language:English
Published: Elsevier 2022-09-01
Series:Pharmacological Research - Modern Chinese Medicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2667142522001166
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author Hui Yang
Zhenyu Wu
Xun Gong
Bo Li
Guangjun Wu
Quan Jiang
author_facet Hui Yang
Zhenyu Wu
Xun Gong
Bo Li
Guangjun Wu
Quan Jiang
author_sort Hui Yang
collection DOAJ
description QingreHuoxue decoction (QRHX) is a well-known traditional Chinese medicine formula for treating rheumatoid arthritis (RA). It is not known how QRHX is involved in bone metabolism regulation and thereby alleviatesbone injury caused by arthritis. In this study, we used collagen-induced arthritis (CIA) rat model to evaluate the effects of QRHX onarthriticdiarthrodial joints and the underlying molecular mechanisms. Our results showed that QRHX significantly reduced foot joint volume, synovial inflammatory infiltration and the arthritis index (AI) score. Micro-CT imaging showed that toe bone and ankle joint were eroded and destroyed progressively during RA process, andcompensatory hyperplasia appeared in late stage RA. QRHX treatment inhibited foot bone erosion of early and mid-stage RA, and improved bone mineral density and trabecular fine structure in late RA.This studyunlocked the whole process details of ankle and toe bone injuryduring RA, as well as the bone metabolic characteristics under QRHX treatmentin CIArats. QRHX was confirmed to inhibite the expression of RANKL and DKK-1 mRNA and protein, enhance the expression of β-catenin. Meanwhile, QRHX reduced the pro-inflammatorycytokines IL-17, IL-1β and TNF-αand upregulated anti-inflammatory IL-4 in serum, improving local and systemic inflammatory microenvironment. These results demonstrated that QRHX had sustained protective effects on diarthrodial joints/bone during RA by a synergistic regulation mechanism, which reverses the imbalance of bone metabolismthroughinhibiting RANKL related osteoclast pathway and promotingWnt/β-catenin related osteoblast activation pathway.
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spelling doaj.art-81149555c099414a9d5614d0939b1acc2022-12-22T01:44:30ZengElsevierPharmacological Research - Modern Chinese Medicine2667-14252022-09-014100156QingreHuoxue decoction protects joint and toe bone morphology and structure in rats with active RA through bidirectional regulation of bone metabolismHui Yang0Zhenyu Wu1Xun Gong2Bo Li3Guangjun Wu4Quan Jiang5Immunology Laboratory, Guang'anmen Hospital, China Academy of Chinese Medical Science, Beijing 100053, ChinaImmunology Laboratory, Guang'anmen Hospital, China Academy of Chinese Medical Science, Beijing 100053, ChinaRheumatism Department, Guang'anmen Hospital, China Academy of Chinese Medical Science, Beijing 100053, ChinaRheumatism Department, Guang'anmen Hospital, China Academy of Chinese Medical Science, Beijing 100053, ChinaImmunology Laboratory, Guang'anmen Hospital, China Academy of Chinese Medical Science, Beijing 100053, ChinaRheumatism Department, Guang'anmen Hospital, China Academy of Chinese Medical Science, Beijing 100053, China; Corresponding author.QingreHuoxue decoction (QRHX) is a well-known traditional Chinese medicine formula for treating rheumatoid arthritis (RA). It is not known how QRHX is involved in bone metabolism regulation and thereby alleviatesbone injury caused by arthritis. In this study, we used collagen-induced arthritis (CIA) rat model to evaluate the effects of QRHX onarthriticdiarthrodial joints and the underlying molecular mechanisms. Our results showed that QRHX significantly reduced foot joint volume, synovial inflammatory infiltration and the arthritis index (AI) score. Micro-CT imaging showed that toe bone and ankle joint were eroded and destroyed progressively during RA process, andcompensatory hyperplasia appeared in late stage RA. QRHX treatment inhibited foot bone erosion of early and mid-stage RA, and improved bone mineral density and trabecular fine structure in late RA.This studyunlocked the whole process details of ankle and toe bone injuryduring RA, as well as the bone metabolic characteristics under QRHX treatmentin CIArats. QRHX was confirmed to inhibite the expression of RANKL and DKK-1 mRNA and protein, enhance the expression of β-catenin. Meanwhile, QRHX reduced the pro-inflammatorycytokines IL-17, IL-1β and TNF-αand upregulated anti-inflammatory IL-4 in serum, improving local and systemic inflammatory microenvironment. These results demonstrated that QRHX had sustained protective effects on diarthrodial joints/bone during RA by a synergistic regulation mechanism, which reverses the imbalance of bone metabolismthroughinhibiting RANKL related osteoclast pathway and promotingWnt/β-catenin related osteoblast activation pathway.http://www.sciencedirect.com/science/article/pii/S2667142522001166Rheumatoid arthritis (RA)QingreHuoxue decoction (QRHX)Bone destructionInflammatory cytokinesBone metabolism
spellingShingle Hui Yang
Zhenyu Wu
Xun Gong
Bo Li
Guangjun Wu
Quan Jiang
QingreHuoxue decoction protects joint and toe bone morphology and structure in rats with active RA through bidirectional regulation of bone metabolism
Pharmacological Research - Modern Chinese Medicine
Rheumatoid arthritis (RA)
QingreHuoxue decoction (QRHX)
Bone destruction
Inflammatory cytokines
Bone metabolism
title QingreHuoxue decoction protects joint and toe bone morphology and structure in rats with active RA through bidirectional regulation of bone metabolism
title_full QingreHuoxue decoction protects joint and toe bone morphology and structure in rats with active RA through bidirectional regulation of bone metabolism
title_fullStr QingreHuoxue decoction protects joint and toe bone morphology and structure in rats with active RA through bidirectional regulation of bone metabolism
title_full_unstemmed QingreHuoxue decoction protects joint and toe bone morphology and structure in rats with active RA through bidirectional regulation of bone metabolism
title_short QingreHuoxue decoction protects joint and toe bone morphology and structure in rats with active RA through bidirectional regulation of bone metabolism
title_sort qingrehuoxue decoction protects joint and toe bone morphology and structure in rats with active ra through bidirectional regulation of bone metabolism
topic Rheumatoid arthritis (RA)
QingreHuoxue decoction (QRHX)
Bone destruction
Inflammatory cytokines
Bone metabolism
url http://www.sciencedirect.com/science/article/pii/S2667142522001166
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