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Food Chem Toxicol. 2018 Oct;120:418-429. doi: 10.1016/j.fct.2018.07.032. Epub 2018 Jul 23.

Thymol inhibits RANKL-induced osteoclastogenesis in RAW264.7 and BMM cells and LPS-induced bone loss in mice.

Author information

1
Department of Dental Pharmacology, School of Dentistry, Institute of Oral Bioscience, Chonbuk National University, Jeon-Ju, 561-756, Republic of Korea.
2
Department of Dental Pharmacology, School of Dentistry, Institute of Oral Bioscience, Chonbuk National University, Jeon-Ju, 561-756, Republic of Korea. Electronic address: ysoh@jbnu.ac.kr.

Abstract

Thymol was identified as one of key compounds contributing to the aroma of thyme leaves. We investigated the effects of thymol on receptor activator NF-κB ligand (RANKL)-induced osteoclastogenesis in murine macrophage RAW264.7 cells and bone marrow derived macrophage (BMMs) cells and lipopolysaccharide (LPS)-induced bone loss in vivo. Thymol markedly reduced RANKL-stimulated osteoclast formation and differentiation in RAW264.7 cells and BMMs cells without any cytotoxic effects. The in vitro and in vivo osteoclastogenesis inhibitory effect of thymol was assessed by calculating the quantity of TRAP (+) multinucleated cells and its inhibitory effects on the resorbing capacity were examined on calcium phosphate-coated plates. Moreover, the inhibitory effects of thymol resulted in a reduction of RANK, cathepsin K, matrix metalloproteinase-9 (MMP-9), dendritic cell-specific transmembrane protein (DC-STAMP), c-terminal myc kinase (C-MYC), C-terminal Src kinase (C-SRC), GRB2-associated-binding protein 2 (GAB2), microphthalmia-associated transcription factor (MITF), and carbonic anhydrase II genes. Similarly, activities of ERK, JNK and AKT and protein expressions of NFATc1, C-FOS, MMP-9 and cathepsin K were downregulated by thymol. More importantly, the application of thymol significantly reduced LPS-induced inflammatory bone loss in mice. In conclusion, these findings identified that thymol could be a useful therapeutic agent for the prevention of bone destructive diseases.

KEYWORDS:

Bone loss; Osteoclast; Osteoporosis; RANKL; Thymol

PMID:
30048646
DOI:
10.1016/j.fct.2018.07.032
[Indexed for MEDLINE]

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