<i>N</i>-[2-(4-Acetyl-1-Piperazinyl)Phenyl]-2-(3-Methylphenoxy)Acetamide (NAPMA) Inhibits Osteoclast Differentiation and Protects against Ovariectomy-Induced Osteoporosis
Osteoclasts are large, multinucleated cells responsible for bone resorption and are induced in response to the regulatory activity of receptor activator of nuclear factor-kappa B ligand (RANKL). Excessive osteoclast activity causes pathological bone loss and destruction. Many studies have investigat...
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MDPI AG
2020-10-01
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| author | Jinkyung Lee Sun-Hee Ahn Zhihao Chen Sohi Kang Dong Kyu Choi Changjong Moon Sang Hyun Min Byung-Ju Park Tae-Hoon Lee |
| author_facet | Jinkyung Lee Sun-Hee Ahn Zhihao Chen Sohi Kang Dong Kyu Choi Changjong Moon Sang Hyun Min Byung-Ju Park Tae-Hoon Lee |
| author_sort | Jinkyung Lee |
| collection | DOAJ |
| description | Osteoclasts are large, multinucleated cells responsible for bone resorption and are induced in response to the regulatory activity of receptor activator of nuclear factor-kappa B ligand (RANKL). Excessive osteoclast activity causes pathological bone loss and destruction. Many studies have investigated molecules that specifically inhibit osteoclast activity by blocking RANKL signaling or bone resorption. In recent years, we screened compounds from commercial libraries to identify molecules capable of inhibiting RANKL-induced osteoclast differentiation. Consequently, we reported some compounds that are effective at attenuating osteoclast activity. In this study, we found that <i>N</i>-[2-(4-acetyl-1-piperazinyl)phenyl]-2-(3-methylphenoxy)acetamide (NAPMA) significantly inhibited the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive cells from bone marrow-derived macrophages in a dose-dependent manner, without cytotoxic effects. NAPMA downregulated the expression of osteoclast-specific markers, such as c-Fos, NFATc1, DC-STAMP, cathepsin K, and MMP-9, at the transcript and protein levels. Accordingly, bone resorption and actin ring formation were decreased in response to NAPMA treatment. Furthermore, we demonstrated the protective effect of NAPMA against ovariectomy-induced bone loss using micro-CT and histological analysis. Collectively, the results showed that NAPMA inhibited osteoclast differentiation and attenuated bone resorption. It is thus a potential drug candidate for the treatment of osteoporosis and other bone diseases associated with excessive bone resorption. |
| first_indexed | 2024-03-10T15:27:41Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T15:27:41Z |
| publishDate | 2020-10-01 |
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| series | Molecules |
| spelling | doaj.art-8ec472c12f6549a1804cd5030d6dc30a2023-11-20T17:56:34ZengMDPI AGMolecules1420-30492020-10-012520485510.3390/molecules25204855<i>N</i>-[2-(4-Acetyl-1-Piperazinyl)Phenyl]-2-(3-Methylphenoxy)Acetamide (NAPMA) Inhibits Osteoclast Differentiation and Protects against Ovariectomy-Induced OsteoporosisJinkyung Lee0Sun-Hee Ahn1Zhihao Chen2Sohi Kang3Dong Kyu Choi4Changjong Moon5Sang Hyun Min6Byung-Ju Park7Tae-Hoon Lee8Department of Oral Biochemistry, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 61186, KoreaDepartment of Bio-Health Research Center, Korea Photonics Technology Institute (KOPTI), Gwangju 61007, KoreaDepartment of Molecular Medicine (BK21plus), Chonnam National University Graduate School, Gwangju 61186, KoreaDepartment of Veterinary Anatomy, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, KoreaNew Drug Development Center, DGMIF, 80 Chumbok-ro, Dong-gu, Daegu 41061, KoreaDepartment of Veterinary Anatomy, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, KoreaNew Drug Development Center, DGMIF, 80 Chumbok-ro, Dong-gu, Daegu 41061, KoreaDepartment of Oral Biochemistry, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 61186, KoreaDepartment of Oral Biochemistry, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 61186, KoreaOsteoclasts are large, multinucleated cells responsible for bone resorption and are induced in response to the regulatory activity of receptor activator of nuclear factor-kappa B ligand (RANKL). Excessive osteoclast activity causes pathological bone loss and destruction. Many studies have investigated molecules that specifically inhibit osteoclast activity by blocking RANKL signaling or bone resorption. In recent years, we screened compounds from commercial libraries to identify molecules capable of inhibiting RANKL-induced osteoclast differentiation. Consequently, we reported some compounds that are effective at attenuating osteoclast activity. In this study, we found that <i>N</i>-[2-(4-acetyl-1-piperazinyl)phenyl]-2-(3-methylphenoxy)acetamide (NAPMA) significantly inhibited the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive cells from bone marrow-derived macrophages in a dose-dependent manner, without cytotoxic effects. NAPMA downregulated the expression of osteoclast-specific markers, such as c-Fos, NFATc1, DC-STAMP, cathepsin K, and MMP-9, at the transcript and protein levels. Accordingly, bone resorption and actin ring formation were decreased in response to NAPMA treatment. Furthermore, we demonstrated the protective effect of NAPMA against ovariectomy-induced bone loss using micro-CT and histological analysis. Collectively, the results showed that NAPMA inhibited osteoclast differentiation and attenuated bone resorption. It is thus a potential drug candidate for the treatment of osteoporosis and other bone diseases associated with excessive bone resorption.https://www.mdpi.com/1420-3049/25/20/4855NAPMAosteoclastovariectomyosteoporosisbone lossbone resorption |
| spellingShingle | Jinkyung Lee Sun-Hee Ahn Zhihao Chen Sohi Kang Dong Kyu Choi Changjong Moon Sang Hyun Min Byung-Ju Park Tae-Hoon Lee <i>N</i>-[2-(4-Acetyl-1-Piperazinyl)Phenyl]-2-(3-Methylphenoxy)Acetamide (NAPMA) Inhibits Osteoclast Differentiation and Protects against Ovariectomy-Induced Osteoporosis Molecules NAPMA osteoclast ovariectomy osteoporosis bone loss bone resorption |
| title | <i>N</i>-[2-(4-Acetyl-1-Piperazinyl)Phenyl]-2-(3-Methylphenoxy)Acetamide (NAPMA) Inhibits Osteoclast Differentiation and Protects against Ovariectomy-Induced Osteoporosis |
| title_full | <i>N</i>-[2-(4-Acetyl-1-Piperazinyl)Phenyl]-2-(3-Methylphenoxy)Acetamide (NAPMA) Inhibits Osteoclast Differentiation and Protects against Ovariectomy-Induced Osteoporosis |
| title_fullStr | <i>N</i>-[2-(4-Acetyl-1-Piperazinyl)Phenyl]-2-(3-Methylphenoxy)Acetamide (NAPMA) Inhibits Osteoclast Differentiation and Protects against Ovariectomy-Induced Osteoporosis |
| title_full_unstemmed | <i>N</i>-[2-(4-Acetyl-1-Piperazinyl)Phenyl]-2-(3-Methylphenoxy)Acetamide (NAPMA) Inhibits Osteoclast Differentiation and Protects against Ovariectomy-Induced Osteoporosis |
| title_short | <i>N</i>-[2-(4-Acetyl-1-Piperazinyl)Phenyl]-2-(3-Methylphenoxy)Acetamide (NAPMA) Inhibits Osteoclast Differentiation and Protects against Ovariectomy-Induced Osteoporosis |
| title_sort | i n i 2 4 acetyl 1 piperazinyl phenyl 2 3 methylphenoxy acetamide napma inhibits osteoclast differentiation and protects against ovariectomy induced osteoporosis |
| topic | NAPMA osteoclast ovariectomy osteoporosis bone loss bone resorption |
| url | https://www.mdpi.com/1420-3049/25/20/4855 |
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