Yougui pills exert osteoprotective effects on rabbit steroid-related osteonecrosis of the femoral head by activating β-catenin

Peng Zhang; Huihui Xu; Pinger Wang; Rui Dong; Chenjie Xia; Zhenyu Shi; Rui Xu; Liang Fang; Zhen Zou; Qinwen Ge; Peijian Tong; Hongting Jin

Biomedicine & Pharmacotherapy (Dec 2019)

Yougui pills exert osteoprotective effects on rabbit steroid-related osteonecrosis of the femoral head by activating β-catenin

Peng Zhang,
Huihui Xu,
Pinger Wang,
Rui Dong,
Chenjie Xia,
Zhenyu Shi,
Rui Xu,
Liang Fang,
Zhen Zou,
Qinwen Ge,
Peijian Tong,
Hongting Jin

Affiliations

Peng Zhang: The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Huihui Xu: The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Pinger Wang: The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Rui Dong: The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Chenjie Xia: The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Zhenyu Shi: The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Rui Xu: The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Liang Fang: The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Zhen Zou: The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Qinwen Ge: The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Peijian Tong: Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; Corresponding author at: The First Affiliated Hospital of Zhejiang Chinese Medical University, No.54, You Dian Road, Hangzhou 310006, Zhejiang, China.
Hongting Jin: The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; Corresponding author at: Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, No.548, Binwen Road, Hangzhou, 310053, Zhejiang, China.

Journal volume & issue: Vol. 120

Abstract

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Objective: To investigate the effect and underlying mechanism of Yougui pills (YGPs) on steroid-related osteonecrosis of the femoral head (SONFH). Methods: Male New Zealand white rabbits were divided into three groups: control group, SONFH group and YGPs group. Rabbit SONFH was induced by methylprednisolone (MPS) combined with lipopolysaccharide (LPS). At 6 weeks post induction, the femoral heads were harvested for tissue analyses, including histopathology, mechanical test of femoral heads, micro-CT, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry for osteocalcin (OCN), vascular endothelial growth factor (VEGF) and β-catenin. Protein levels of cathepsin K (CTSK), phospho-glycogen synthase kinase-3 beta (p-Ser9 GSK-3β) and total glycogen synthase kinase-3 beta (GSK-3β) in femoral heads were also detected. Additionally, the serum TRAP activity was measured using enzyme-linked immunosorbent assay (ELISA). Finally, the effects of YGPs treatment on osteoclast differentiation and osteoblast formation were evaluated in vitro. Results: The ratio of empty lacuna was markedly lower in YGPs group than SONFH group. Micro-CT evaluation indicated that YGPs has a preventive effect on bone loss in rabbit SONFH. YGPs treatment could suppress bone resorption by reducing TRAP+ osteoclast and serum TRACP5b levels in necrotic femoral heads. Moreover, YGPs treatment could promote bone formation by up-regulating the expression of OCN, VEGF and β-catenin, while increasing load-bearing capacity of femoral heads. Interestingly, p-Ser9 GSK-3β downregulation, and CTSK upregulation in necrotic femoral head could be reversed by YGPs treatment, which also effectively inhibited RANKL-induced osteoclast differentiation and promoted osteoblast formation in vitro. Conclusion: YGPs could suppress osteoclastogenesis and promote bone formation during SONFH in rabbits by activating β-catenin.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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