Britanin inhibits titanium wear particle‑induced osteolysis and osteoclastogenesis

Kim,Ju Ang; Lim,Soomin; Ihn,Hye Jung; Kim,Jung-Eun; Yea,Kyungmoo; Moon,Jimin; Choi,Hyukjae; Park,Eui Kyun

doi:10.3892/mmr.2023.13092

Britanin inhibits titanium wear particle‑induced osteolysis and osteoclastogenesis

Authors:
- Ju Ang Kim
- Soomin Lim
- Hye Jung Ihn
- Jung-Eun Kim
- Kyungmoo Yea
- Jimin Moon
- Hyukjae Choi
- Eui Kyun Park
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Affiliations: Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Institute for Hard Tissue and Bio‑tooth Regeneration, Kyungpook National University, Daegu 41940, Republic of Korea, Cell and Matrix Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea, Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea, Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Republic of Korea, College of Pharmacy, Research Institution of Cell Culture, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea
Published online on: September 18, 2023 https://doi.org/10.3892/mmr.2023.13092
Article Number: 205
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Wear particle‑induced osteolysis is a serious complication that occurs in individuals with titanium (Ti)‑based implants following long‑term usage due to loosening of the implants. The control of excessive osteoclast differentiation and inflammation is essential for protecting against wear particle‑induced osteolysis. The present study evaluated the effect of britanin, a pseudoguaianolide sesquiterpene isolated from Inula japonica, on osteoclastogenesis in vitro and Ti particle‑induced osteolysis in vivo. The effect of britanin was examined in the osteoclastogenesis of mouse bone marrow‑derived macrophages (BMMs) using TRAP staining, RT‑PCR, western blotting and immunocytochemistry. The protective effect of britanin was examined in a mouse calvarial osteolysis model and evaluated using micro‑CT and histomorphometry. Britanin inhibited osteoclast differentiation and F‑actin ring formation in the presence of macrophage colony‑stimulating factor and receptor activator of nuclear factor kB ligand in BMMs. The expression of osteoclast‑specific marker genes, including tartrate‑resistant acid phosphatase, cathepsin K, dendritic cell‑specific transmembrane protein, matrix metallopeptidase 9 and nuclear factor of activated T‑cells cytoplasmic 1, in the BMMs was significantly reduced by britanin. In addition, britanin reduced the expression of B lymphocyte‑induced maturation protein‑1, which is a transcriptional repressor of negative osteoclastogenesis regulators, including interferon regulatory factor‑8 and B‑cell lymphoma 6. Conversely, britanin increased the expression levels of anti‑oxidative stress genes, namely nuclear factor erythroid‑2‑related factor 2, NAD(P)H quinone oxidoreductase 1 and heme oxygenase 1 in the BMMs. Furthermore, the administration of britanin significantly reduced osteolysis in a Ti particle‑induced calvarial osteolysis mouse model. Based on these findings, it is suggested that britanin may be a potential therapeutic agent for wear particle‑induced osteolysis and osteoclast‑associated disease.

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