Kaempferol Inhibits IL-1β-Stimulated, RANKL-mediated Osteoclastogenesis via Downregulation of MAPKs, c-Fos, and NFATc1

• Published in: Inflammation Vol. 37; no. 4; pp. 1221 - 1230
• Main Authors: Lee, Won-Seok, Lee, Eun-Gyeong, Sung, Myung-Soon, Yoo, Wan-Hee
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.08.2014
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Bone Marrow Cells - cytology; Bone Resorption; Cell Differentiation; Cell Survival; Cells, Cultured; Down-Regulation; Immunology; Inflammation - metabolism; Interleukin-1beta - pharmacology; Internal Medicine; Kaempferols - chemistry; Male; MAP Kinase Signaling System; Mice; Mice, Inbred ICR; NFATC Transcription Factors - metabolism; Osteoclasts - cytology; Osteoclasts - metabolism; Pathology; Pharmacology/Toxicology; Phosphorylation; Proto-Oncogene Proteins c-fos - metabolism; RANK Ligand - metabolism; Rheumatology; RANK ligand; kaempferol; osteoclastogenesis; interleukin-1β
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-014-9849-6

Kaempferol is one of the most common flavonoid that is present in a variety of vegetables and fruits and has effects on bone metabolism. The present study was performed to define the effects of kaempferol on interleukin (IL)-1β-stimulated receptor activator of NF-κB ligand (RANKL)-mediated osteoclast differentiation. Bone marrow cells were harvested from 6-week-old male imprinting control region mice, and the differentiation of osteoclasts from these cells was evaluated by tartrate-resistant acid phosphatase staining and resorption pit formation assay. Phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated p38, phosphorylated c-Jun amino-terminal kinase, NF-κB (p65), IκBα, c-Fos, and nuclear factor of activated T cells c1 (NFATc1) expressions were examined by Western blotting and quantitative RT-PCR. Kaempferol inhibits IL-1β-stimulated, RANKL-mediated osteoclast differentiation and also inhibits IL-1β-stimulated, RANKL-mediated phosphorylation of ERK 1/2, p38 and JNK MAP kinases, and expressions of c-Fos and NFATc1. These results indicate that kaempferol has an inhibitory role in the bone loss by preventing osteoclast formation and suggest that it might be a novel therapeutic agent for the treatment of inflammatory arthritis by managing bone destruction.