دورية أكاديمية
PF-3845, a Fatty Acid Amide Hydrolase Inhibitor, Directly Suppresses Osteoclastogenesis through ERK and NF-κB Pathways In Vitro and Alveolar Bone Loss In Vivo
| العنوان: | PF-3845, a Fatty Acid Amide Hydrolase Inhibitor, Directly Suppresses Osteoclastogenesis through ERK and NF-κB Pathways In Vitro and Alveolar Bone Loss In Vivo |
|---|---|
| المؤلفون: | Hye-Jung Ihn, Yi-Seul Kim, Soomin Lim, Jong-Sup Bae, Jae-Chang Jung, Yeo-Hyang Kim, Jin-Woo Park, Zhao Wang, Jeong-Tae Koh, Yong-Chul Bae, Moon-Chang Baek, Eui-Kyun Park |
| المصدر: | International Journal of Molecular Sciences, Vol 22, Iss 4, p 1915 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | PF-3845, osteoclastogenesis, bone resorption, alveolar bone loss, ERK, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Alveolar bone loss, the major feature of periodontitis, results from the activation of osteoclasts, which can consequently cause teeth to become loose and fall out; the development of drugs capable of suppressing excessive osteoclast differentiation and function is beneficial for periodontal disease patients. Given the difficulties associated with drug discovery, drug repurposing is an efficient approach for identifying alternative uses of commercially available compounds. Here, we examined the effects of PF-3845, a selective fatty acid amide hydrolase (FAAH) inhibitor, on receptor activator of nuclear factor kappa B ligand (RANKL)-mediated osteoclastogenesis, its function, and the therapeutic potential for the treatment of alveolar bone destruction in experimental periodontitis. PF-3845 significantly suppressed osteoclast differentiation and decreased the induction of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and the expression of osteoclast-specific markers. Actin ring formation and osteoclastic bone resorption were also reduced by PF-3845, and the anti-osteoclastogenic and anti-resorptive activities were mediated by the suppression of phosphorylation of rapidly accelerated fibrosarcoma (RAF), mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase, (ERK) and nuclear factor κB (NF-κB) inhibitor (IκBα). Furthermore, the administration of PF-3845 decreased the number of osteoclasts and the amount of alveolar bone destruction caused by ligature placement in experimental periodontitis in vivo. The present study provides evidence that PF-3845 is able to suppress osteoclastogenesis and prevent alveolar bone loss, and may give new insights into its role as a treatment for osteoclast-related diseases. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 22041915 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/22/4/1915; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms22041915 |
| URL الوصول: | https://doaj.org/article/e5670b82c8f74aca889fef5df70f45c4 |
| رقم الأكسشن: | edsdoj.5670b82c8f74aca889fef5df70f45c4 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 22041915 14220067 16616596 |
|---|---|
| DOI: | 10.3390/ijms22041915 |