Yougui Pills Attenuate Cartilage Degeneration via Activation of TGF-β/Smad Signaling in Chondrocyte of Osteoarthritic Mouse Model

Yougui pills (YGPs) have been used for centuries in the treatment of Chinese patients with Kidney-Yang Deficiency Syndrome. Despite the fact that the efficiency of YGPs on treating osteoarthritis has been verified in clinic, the underlying mechanisms are not totally understood. The present study obs...

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Main Authors: Lei Zhang, Ping-er Wang, Jun Ying, Xing Jin, Cheng Luo, Taotao Xu, Shibing Xu, Rui Dong, Luwei Xiao, Peijian Tong, Hongting Jin
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-09-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fphar.2017.00611/full
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author Lei Zhang
Lei Zhang
Ping-er Wang
Jun Ying
Jun Ying
Xing Jin
Xing Jin
Cheng Luo
Cheng Luo
Taotao Xu
Taotao Xu
Shibing Xu
Shibing Xu
Rui Dong
Rui Dong
Luwei Xiao
Peijian Tong
Hongting Jin
author_facet Lei Zhang
Lei Zhang
Ping-er Wang
Jun Ying
Jun Ying
Xing Jin
Xing Jin
Cheng Luo
Cheng Luo
Taotao Xu
Taotao Xu
Shibing Xu
Shibing Xu
Rui Dong
Rui Dong
Luwei Xiao
Peijian Tong
Hongting Jin
author_sort Lei Zhang
collection DOAJ
description Yougui pills (YGPs) have been used for centuries in the treatment of Chinese patients with Kidney-Yang Deficiency Syndrome. Despite the fact that the efficiency of YGPs on treating osteoarthritis has been verified in clinic, the underlying mechanisms are not totally understood. The present study observes the therapeutic role of YGPs and mechanisms underlying its chondroprotective action in osteoarthritic cartilage. To evaluate the chondroprotective effects of YGPs, we examined the impact of orally administered YGPs in a model of destabilization of the medial meniscus (DMM). Male C57BL/6J mice were provided a daily treatment of YGPs and a DMM surgery was performed on the right knee. At 12 weeks post-surgery, the joints were harvested for tissue analyses, including histomorphometry, OARSI scoring, micro-CT and immunohistochemistry for COL-2, MMP-13 and pSMAD-2. We also performed the relative experiments mentioned above in mice with Tgfbr2 conditional knockout (TGF-βRIICol2ER mice) in articular cartilage. To evaluate the safety of YGPs, hematology was determined in each group. Amelioration of cartilage degradation was observed in the YGPs group, with increases in cartilage area and thickness, proteoglycan matrix, and decreases in OARSI score at 12 weeks post surgery. In addition, reduced BV/TV and Tb. Th, and elevated Tb. Sp were observed in DMM-induced mice followed by YGPs treatment. Moreover, the preservation of cartilage correlated with reduced MMP-13, and elevated COL-2 and pSMAD-2 protein expressional levels were also revealed in DMM-induced mice treated with YGPs. Similarly, TGF-βRIICol2ER mice exhibited significant OA-like phenotype. However, no significant difference in cartilage structure was observed in TGF-βRIICol2ER mice after YGPs treatment. Interestingly, no obvious adverse effects were observed in mice from each group based on the hematologic analyses. These findings suggested that YGPs could inhibit cartilage degradation through enhancing TGF-β/Smad signaling activation, and be considered a good option for the treatment of osteoarthritis.
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spelling doaj.art-53dbf8e7f4414f6b9250872c9c6830412022-12-22T00:19:47ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-09-01810.3389/fphar.2017.00611289293Yougui Pills Attenuate Cartilage Degeneration via Activation of TGF-β/Smad Signaling in Chondrocyte of Osteoarthritic Mouse ModelLei Zhang0Lei Zhang1Ping-er Wang2Jun Ying3Jun Ying4Xing Jin5Xing Jin6Cheng Luo7Cheng Luo8Taotao Xu9Taotao Xu10Shibing Xu11Shibing Xu12Rui Dong13Rui Dong14Luwei Xiao15Peijian Tong16Hongting Jin17Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou, ChinaThe First College of Clinical Medicine, Zhejiang Chinese Medical UniversityHangzhou, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou, ChinaThe First College of Clinical Medicine, Zhejiang Chinese Medical UniversityHangzhou, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou, ChinaDepartment of Orthopaedics and Traumatology, Wangjiang Sub-District Community Health Service CenterHangzhou, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou, ChinaThe First College of Clinical Medicine, Zhejiang Chinese Medical UniversityHangzhou, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou, ChinaThe First College of Clinical Medicine, Zhejiang Chinese Medical UniversityHangzhou, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou, ChinaThe First College of Clinical Medicine, Zhejiang Chinese Medical UniversityHangzhou, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou, ChinaThe First College of Clinical Medicine, Zhejiang Chinese Medical UniversityHangzhou, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou, ChinaDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou, ChinaYougui pills (YGPs) have been used for centuries in the treatment of Chinese patients with Kidney-Yang Deficiency Syndrome. Despite the fact that the efficiency of YGPs on treating osteoarthritis has been verified in clinic, the underlying mechanisms are not totally understood. The present study observes the therapeutic role of YGPs and mechanisms underlying its chondroprotective action in osteoarthritic cartilage. To evaluate the chondroprotective effects of YGPs, we examined the impact of orally administered YGPs in a model of destabilization of the medial meniscus (DMM). Male C57BL/6J mice were provided a daily treatment of YGPs and a DMM surgery was performed on the right knee. At 12 weeks post-surgery, the joints were harvested for tissue analyses, including histomorphometry, OARSI scoring, micro-CT and immunohistochemistry for COL-2, MMP-13 and pSMAD-2. We also performed the relative experiments mentioned above in mice with Tgfbr2 conditional knockout (TGF-βRIICol2ER mice) in articular cartilage. To evaluate the safety of YGPs, hematology was determined in each group. Amelioration of cartilage degradation was observed in the YGPs group, with increases in cartilage area and thickness, proteoglycan matrix, and decreases in OARSI score at 12 weeks post surgery. In addition, reduced BV/TV and Tb. Th, and elevated Tb. Sp were observed in DMM-induced mice followed by YGPs treatment. Moreover, the preservation of cartilage correlated with reduced MMP-13, and elevated COL-2 and pSMAD-2 protein expressional levels were also revealed in DMM-induced mice treated with YGPs. Similarly, TGF-βRIICol2ER mice exhibited significant OA-like phenotype. However, no significant difference in cartilage structure was observed in TGF-βRIICol2ER mice after YGPs treatment. Interestingly, no obvious adverse effects were observed in mice from each group based on the hematologic analyses. These findings suggested that YGPs could inhibit cartilage degradation through enhancing TGF-β/Smad signaling activation, and be considered a good option for the treatment of osteoarthritis.http://journal.frontiersin.org/article/10.3389/fphar.2017.00611/fullYougui pillsosteoarthritisconditional knockoutcartilage protectiveTGF-β/Smad signaling
spellingShingle Lei Zhang
Lei Zhang
Ping-er Wang
Jun Ying
Jun Ying
Xing Jin
Xing Jin
Cheng Luo
Cheng Luo
Taotao Xu
Taotao Xu
Shibing Xu
Shibing Xu
Rui Dong
Rui Dong
Luwei Xiao
Peijian Tong
Hongting Jin
Yougui Pills Attenuate Cartilage Degeneration via Activation of TGF-β/Smad Signaling in Chondrocyte of Osteoarthritic Mouse Model
Frontiers in Pharmacology
Yougui pills
osteoarthritis
conditional knockout
cartilage protective
TGF-β/Smad signaling
title Yougui Pills Attenuate Cartilage Degeneration via Activation of TGF-β/Smad Signaling in Chondrocyte of Osteoarthritic Mouse Model
title_full Yougui Pills Attenuate Cartilage Degeneration via Activation of TGF-β/Smad Signaling in Chondrocyte of Osteoarthritic Mouse Model
title_fullStr Yougui Pills Attenuate Cartilage Degeneration via Activation of TGF-β/Smad Signaling in Chondrocyte of Osteoarthritic Mouse Model
title_full_unstemmed Yougui Pills Attenuate Cartilage Degeneration via Activation of TGF-β/Smad Signaling in Chondrocyte of Osteoarthritic Mouse Model
title_short Yougui Pills Attenuate Cartilage Degeneration via Activation of TGF-β/Smad Signaling in Chondrocyte of Osteoarthritic Mouse Model
title_sort yougui pills attenuate cartilage degeneration via activation of tgf β smad signaling in chondrocyte of osteoarthritic mouse model
topic Yougui pills
osteoarthritis
conditional knockout
cartilage protective
TGF-β/Smad signaling
url http://journal.frontiersin.org/article/10.3389/fphar.2017.00611/full
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