Puerarin Specifically Disrupts Osteoclast Activation Via Blocking Integrin-β3 Pyk2/Src/Cbl Signaling Pathway

Overview

Journal J Orthop Translat

Publisher Elsevier

Specialty Orthopedics

Date 2022 Mar 1

PMID 35228997

Authors

Zuocheng Qiu

Ling Li

Yuying Huang

Keda Shi

Lizhong Zhang

Cuishan Huang

Jiechao Liang

Qingqiang Zeng

Jiali Wang

Xiangjiu He

Ling Qin

Xinluan Wang

Affiliations

Soon will be listed here.

Abstract

Objective: Given the limitations of current anti-resorption agents for postmenopausal osteoporosis, there is a need for alternatives without impairing coupling crosstalk between bone resorption and bone formation ie. osteoclastogenesis. Puerarin, a unique C-glycoside isoflavonoid, was found to be able to prevent bone loss by inhibiting bone resorption, but the underlying mechanism was controversial. In this study, we investigated the effects of puerarin on osteoclastic differentiation, activation and bone resorption and its underlying molecular mechanism , and then evaluated the effects of puerarin on bone metabolism using an ovariectomized (OVX) rat model.

Methods: , the effect of puerarin on osteoclastic cytotoxicity, differentiation, apoptosis, activation and function were studied in raw 264.7 cells and mouse BMMs. Mechanistically, osteoclast-related makers were determined by RT-PCR, western blot, immunofluorescence, and kinase activity assay. , Micro-CT, histology, serum bone biomarker, and mechanical testing were used to evaluate the effects of puerarin on preventing osteoporosis.

Results: Puerarin significantly inhibited osteoclast activation and bone resorption, without affecting osteoclastogenesis or apoptosis. In terms of mechanism, the expressions of protein of integrin-β3 and phosphorylations of Src, Pyk2 and Cbl were lower in puerarin group than those in the control group. Oral administration of puerarin prevented OVX-induced trabecular bone loss and significantly improved bone strength in rats. Moreover, puerarin significantly decreased trap positive osteoclast numbers and serum TRAP-5b, CTx1, without affecting bone formation rate.

Conclusions: Collectively, puerarin prevented the bone loss in OVX rat through suppression of osteoclast activation and bone resorption, by inhibiting integrin-β3-Pyk2/Cbl/Src signaling pathway, without affecting osteoclasts formation or apoptosis.

Translational Potential Of This Article: These results demonstrate the unique mechanism of puerarin on bone metabolism and provide a novel agent for prevention of postmenopausal osteoporosis.

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