Bushenhuoxue formula promotes osteogenic differentiation of growth plate chondrocytes through β-catenin-dependent manner during osteoporosis

Chenjie Xia; Zhen Zou; Liang Fang; Qinwen Ge; Peng Zhang; Huihui Xu; Rui Xu; Zhenyu Shi; Houfu Lin; Xinyi Ding; Luwei Xiao; Peijian Tong; Ping-er Wang; Hongting Jin

Biomedicine & Pharmacotherapy (Jul 2020)

Bushenhuoxue formula promotes osteogenic differentiation of growth plate chondrocytes through β-catenin-dependent manner during osteoporosis

Chenjie Xia,
Zhen Zou,
Liang Fang,
Qinwen Ge,
Peng Zhang,
Huihui Xu,
Rui Xu,
Zhenyu Shi,
Houfu Lin,
Xinyi Ding,
Luwei Xiao,
Peijian Tong,
Ping-er Wang,
Hongting Jin

Affiliations

Chenjie Xia: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China; Department of Orthopedic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, China
Zhen Zou: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
Liang Fang: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
Qinwen Ge: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
Peng Zhang: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
Huihui Xu: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
Rui Xu: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
Zhenyu Shi: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
Houfu Lin: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
Xinyi Ding: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
Luwei Xiao: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Peijian Tong: Department of Orthopedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Ping-er Wang: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; Corresponding authors at: Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, No.548, Binwen Road, Hangzhou, Zhejiang Province, 310053, China.
Hongting Jin: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; Corresponding authors at: Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, No.548, Binwen Road, Hangzhou, Zhejiang Province, 310053, China.

Journal volume & issue: Vol. 127
p. 110170

Abstract

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Background: Bushenhuoxue formula (BSHXF) has shown excellent clinical effects on the treatment of osteoporosis in China. The aim of this study is to determine the anti-osteoporosis effects and precise molecular mechanisms of BSHXF on mouse models. Methods: Ten-week-old female C57BL/6 J mice were subjected to ovariectomy and provided a daily treatment of BSHXF. At 8 weeks post-surgery, the femurs were harvested for tissue analyses including μCT, histology, qRT-PCR and immunohistochemical (IHC) staining of β-catenin, ALP and FABP4. To investigate the role of β-catenin in the anti-osteoporosis effects of BSHXF, relative experiments mentioned above were performed in β-catenin conditional knockout mice. Results: Ovariectomized (OVX) mice presented severe bone loss and excessive fat accumulation in the chondro-osseous junction underneath the growth plate, with decreased expression of ALP and increased expression of FABP4. BSHXF significantly recovered the OVX-induced abnormal osteogenesis and adipogenesis with the activation of β-catenin in growth plate chondrocytes. Further, we generated growth plate chondrocyte-specific β-catenin knockout (β-cateninGli1ER) mice that exhibited bone loss and fat accumulation in the chondro-osseous junction, similar to the OVX mice. However, BSHXF failed to rescue the osteoporosis-like phenotype in β-cateninGli1ER mice, indicating the anti-osteoporosis effects of BSHXF act mainly through β-catenin signaling. No significant restoration of ALP and FABP4 was observed in β-cateninGli1ER mice after the treatment of BSHXF. Conclusions: BSHXF attenuates osteoporosis by promoting osteogenic differentiation of growth plate chondrocytes mainly in β-catenin-dependent manner. BSHXF is considered as a new candidate for the treatment of osteoporosis.

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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