β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling Pathways
Osteoporosis is a systemic metabolic bone disorder that is caused by an imbalance in the functions of osteoclasts and osteoblasts and is characterized by excessive bone resorption by osteoclasts. Targeting osteoclast differentiation and bone resorption is considered a good fundamental solution for o...
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2021-05-01
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author | Gyeong Do Park Yoon-Hee Cheon So Young Eun Chang Hoon Lee Myeung Su Lee Ju-Young Kim Hae Joong Cho |
author_facet | Gyeong Do Park Yoon-Hee Cheon So Young Eun Chang Hoon Lee Myeung Su Lee Ju-Young Kim Hae Joong Cho |
author_sort | Gyeong Do Park |
collection | DOAJ |
description | Osteoporosis is a systemic metabolic bone disorder that is caused by an imbalance in the functions of osteoclasts and osteoblasts and is characterized by excessive bone resorption by osteoclasts. Targeting osteoclast differentiation and bone resorption is considered a good fundamental solution for overcoming bone diseases. β-boswellic acid (βBA) is a natural compound found in <i>Boswellia serrata</i>, which is an active ingredient with anti-inflammatory, anti-rheumatic, and anti-cancer effects. Here, we explored the anti-resorptive effect of βBA on osteoclastogenesis. βBA significantly inhibited the formation of tartrate-resistant acid phosphatase-positive osteoclasts induced by receptor activator of nuclear factor-B ligand (RANKL) and suppressed bone resorption without any cytotoxicity. Interestingly, βBA significantly inhibited the phosphorylation of IκB, Btk, and PLCγ2 and the degradation of IκB. Additionally, βBA strongly inhibited the mRNA and protein expression of c-Fos and NFATc1 induced by RANKL and subsequently attenuated the expression of osteoclast marker genes, such as <i>OC-STAMP, DC-STAMP, β3-integrin, MMP9, ATP6v0d2,</i> and <i>CtsK</i>. These results suggest that βBA is a potential therapeutic candidate for the treatment of excessive osteoclast-induced bone diseases such as osteoporosis. |
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language | English |
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spelling | doaj.art-04e300d807d348bbb5574807b4bd57a32023-11-21T18:08:26ZengMDPI AGMolecules1420-30492021-05-01269266510.3390/molecules26092665β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling PathwaysGyeong Do Park0Yoon-Hee Cheon1So Young Eun2Chang Hoon Lee3Myeung Su Lee4Ju-Young Kim5Hae Joong Cho6Musculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaMusculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaMusculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaMusculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaMusculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaMusculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaMusculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaOsteoporosis is a systemic metabolic bone disorder that is caused by an imbalance in the functions of osteoclasts and osteoblasts and is characterized by excessive bone resorption by osteoclasts. Targeting osteoclast differentiation and bone resorption is considered a good fundamental solution for overcoming bone diseases. β-boswellic acid (βBA) is a natural compound found in <i>Boswellia serrata</i>, which is an active ingredient with anti-inflammatory, anti-rheumatic, and anti-cancer effects. Here, we explored the anti-resorptive effect of βBA on osteoclastogenesis. βBA significantly inhibited the formation of tartrate-resistant acid phosphatase-positive osteoclasts induced by receptor activator of nuclear factor-B ligand (RANKL) and suppressed bone resorption without any cytotoxicity. Interestingly, βBA significantly inhibited the phosphorylation of IκB, Btk, and PLCγ2 and the degradation of IκB. Additionally, βBA strongly inhibited the mRNA and protein expression of c-Fos and NFATc1 induced by RANKL and subsequently attenuated the expression of osteoclast marker genes, such as <i>OC-STAMP, DC-STAMP, β3-integrin, MMP9, ATP6v0d2,</i> and <i>CtsK</i>. These results suggest that βBA is a potential therapeutic candidate for the treatment of excessive osteoclast-induced bone diseases such as osteoporosis.https://www.mdpi.com/1420-3049/26/9/2665β-boswellic acidosteoclastbone resorptionosteoporosis |
spellingShingle | Gyeong Do Park Yoon-Hee Cheon So Young Eun Chang Hoon Lee Myeung Su Lee Ju-Young Kim Hae Joong Cho β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling Pathways Molecules β-boswellic acid osteoclast bone resorption osteoporosis |
title | β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling Pathways |
title_full | β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling Pathways |
title_fullStr | β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling Pathways |
title_full_unstemmed | β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling Pathways |
title_short | β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling Pathways |
title_sort | β boswellic acid inhibits rankl induced osteoclast differentiation and function by attenuating nf κb and btk plcγ2 signaling pathways |
topic | β-boswellic acid osteoclast bone resorption osteoporosis |
url | https://www.mdpi.com/1420-3049/26/9/2665 |
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