Ugonin L inhibits osteoclast formation and promotes osteoclast apoptosis by inhibiting the MAPK and NF-κB pathways - 13/09/23

Doi : 10.1016/j.biopha.2023.115392

Chun-Lin Liu ^a,^b,^{^{1
These authors contributed equally to this work.}}, Trung-Loc Ho ^a,^{^{1
These authors contributed equally to this work.}}, Shuen-Yih Fang ^c, Jeng-Hung Guo ^a,^b, Chih-Ying Wu ^b,^d,^e, Yi-Chin Fong ^f,^g,^h, Chih-Chuang Liaw ^c,^i,^⁎ , Chih-Hsin Tang ^a,^j,^k,^l,^m,^⁎
^a Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
^b Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan
^c Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan
^d Graduate Institute of Integrated Medicine, China Medical University, Taiwan
^e Department of Neurosurgery, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
^f Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
^g Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
^h Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan
ⁱ Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan
^j Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
^k Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
^l Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan
^m Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan

^⁎Corresponding author at: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan.Department of Marine Biotechnology and Resources, National Sun Yat-sen UniversityKaohsiungTaiwan^⁎⁎Corresponding author at: Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.Graduate Institute of Biomedical Sciences, China Medical UniversityTaichungTaiwan

Abstract

Bone loss is a major issue for patients with osteoporosis, arthritis, periodontitis, and bone metastasis; however, anti-resorption drugs used to treat bone loss have been linked to a variety of adverse effects. Helminthostachys zeylanica (L.) Hook, belonging to the family Ophioglossaceae, is commonly used in traditional Chinese medicine to treat inflammation and liver problems. In the current study, ugonin L extracted from H. zeylanica was shown to reduce the receptor activator of nuclear factor kappa beta ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells in a concentration-dependent manner. Ugonin L treatment also inhibited the mRNA expression of osteoclast markers. Ugonin L was also shown to promote cell apoptosis in mature osteoclasts and suppress RANKL-induced ERK, p38, JNK, and NF-κB activation. Taken together, ugonin L appears to be a promising candidate for the development of novel anti-resorption therapies.

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Highlights

•	Ugonin L attenuated RANKL-stimulated osteoclast formation and osteoclast-specific gene expression.
•	Ugonin L reduced bone resorption activity and increased cell apoptosis in mature osteoclast.
•	Ugonin L significantly inhibited RANKL-induced MAPKs and NF-κB pathways.

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Abbreviations : RANKL, ERK, JNK, p38 MAPK, IKK, NF-κB, Acp5, Cts-K, ATP6V1A, MMP9, NFATC1, ALP, BMP-2, COL1A, OPN, Runx2, DAPI, F-actin, GEO, IPA, BSA, RIPA, SDS-PAGE, TBST

Keywords : Ugonin L, Osteoclast, RANKL, Bone resorption, Apoptosis

Plan

Introduction

Materials and methods

Materials

Cell cultures

GEO database analysis

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays

Quantitative real-time PCR

Osteoclast differentiation

Analysis of bone resorption activity

Western blot analysis

Immunofluorescence staining

NF-κB reporter assay

Statistics

Results

Ugonin L inhibits osteoclastogenesis

Ugonin L inhibits bone resorption activity and induces apoptosis in mature osteoclasts

Ugonin L suppresses the MPAKs and NF-κB signaling pathways

Discussion

CRediT authorship contribution statement

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Article 115392- octobre 2023 Retour au numéro

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Ugonin L inhibits osteoclast formation and promotes osteoclast apoptosis by inhibiting the MAPK and NF-κB pathways - 13/09/23

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