Isobavachalcone inhibits RANKL-induced osteoclastogenesis via miR-193-3p/NF-κB/NFATc1 signaling pathway in BMMs cells

Author:

Liu Xin1,Xu Xiaosa1,Li Jinping12,Shi Liying1,Zeng Ying3,Tang Siyuan4,Liu Wei4,Jia Lujuan1,Li Yuhong1,Zhang Jie5

Affiliation:

1. Department of Pharmachemistry, Xiangya School of Pharmaceutical Sciences, Central South University , Chang Sha, Hunan , China

2. Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Central South University , Chang Sha, Hunan , China

3. Department of Cardiovascular Medicine, The First Hospital of Hunan University of Traditional Chinese Medicine , Chang Sha, Hunan , China

4. Department of Community Nursing, Central South University , Changsha, Hunan , China

5. Pharmacy Department, The Third Xiangya Hospital of Central South University , Changsha, Hunan , China

Abstract

ABSTRACT Inhibition of extensive osteoclastogenesis and bone resorption is considered a potential therapeutic target for the treatment of osteoporosis. Isobavachalcone (IBC) is derived from the traditional Chinese herb Psoralea corylifolia Linn. We showed that IBC dose-dependently suppressed receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis in bone marrow monocyte/macrophage (BMMs) and osteoclastic bone-resorption function without cytotoxicity at a dose of no more than 8 µmin vitro. Mechanistically, the results of western blot and quantitative real-time polymerase chain reaction (qRT-PCR) indicated that IBC inhibited the RANKL-induced degradation of IκBα and phosphorylation of nuclear factor kappa B (NF-κB) in BMMs, and subsequently downregulated the expression of osteoclastic-specific genes and osteoclastogenesis-related proteins. TRAP staining and qRT-PCR showed that IBC can inhibit osteoclast differentiation by down-regulating the expression of miR-193-3p on osteoclast differentiation. Overall, our findings suggest that IBC may serve as a promising compound for the treatment of osteoporosis and other metabolic bone diseases.

Funder

Natural Science Foundation of China

Natural Science Foundation of Hunan Province

N Hunan Province, China

Publisher

Oxford University Press (OUP)

Subject

Organic Chemistry,Molecular Biology,Applied Microbiology and Biotechnology,General Medicine,Biochemistry,Analytical Chemistry,Biotechnology

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4. Osteoclast differentiation and activation;Boyle;Nature,2003

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