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

Abstract

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.

• Authors: Peng Zhang, Huihui Xu, Pinger Wang, Rui Dong, Chenjie Xia, Zhenyu Shi, Rui Xu, Liang Fang, Zhen Zou, Qinwen Ge, Peijian Tong, Hongting Jin
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 120 Pg. 109520 (Dec 2019) ISSN: 1950-6007 [Electronic] France
• PMID: 31629251 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• Glucocorticoids
• Lipopolysaccharides
• beta Catenin
• yougui
• Methylprednisolone

Topics

• Animals
• Cell Line
• Drugs, Chinese Herbal (pharmacology)
• Femur Head Necrosis (prevention & control)
• Gene Expression Regulation (drug effects)
• Glucocorticoids (administration & dosage, toxicity)
• Lipopolysaccharides (administration & dosage, toxicity)
• Male
• Methylprednisolone (administration & dosage, toxicity)
• Mice
• Osteogenesis (drug effects)
• Osteonecrosis (prevention & control)
• Rabbits
• Random Allocation
• beta Catenin (genetics, metabolism)