α-Linolenic Acid Inhibits RANKL-Induced Osteoclastogenesis In Vitro and Prevents Inflammation In Vivo
Inflammation is an important risk factor for bone-destroying diseases. Our preliminary research found that <i>Zanthoxylum bungeanum</i> seed oil (ZBSO) is abundant in unsaturated fatty acids and could inhibit osteoclastogenesis in receptor activator of nuclear factor κB ligand (RANKL)-in...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | Foods |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2304-8158/12/3/682 |
| _version_ | 1797624551565164544 |
|---|---|
| author | Yufeng Deng Weizhou Li Yingying Zhang Jingjing Li Fangting He Ke Dong Zehui Hong Ruocheng Luo Xiaofang Pei |
| author_facet | Yufeng Deng Weizhou Li Yingying Zhang Jingjing Li Fangting He Ke Dong Zehui Hong Ruocheng Luo Xiaofang Pei |
| author_sort | Yufeng Deng |
| collection | DOAJ |
| description | Inflammation is an important risk factor for bone-destroying diseases. Our preliminary research found that <i>Zanthoxylum bungeanum</i> seed oil (ZBSO) is abundant in unsaturated fatty acids and could inhibit osteoclastogenesis in receptor activator of nuclear factor κB ligand (RANKL)-induced RAW264.7 cells. However, the key constituents in ZBSO in the prevention of osteoclastogenesis and its possible mechanism related to inflammation are still unclear. Therefore, in this study, oleic acid (OA), linoleic acid (LA), palmitoleic acid (PLA), and alpha-linolenic acid (ALA) in ZBSO, havingthe strongest effect on RANKL-induced osteoclastogenesis, were selected by a tartrate-resistant acid phosphatase (TRAP) staining method. Furthermore, the effects of the selected fatty acids on anti-inflammation and anti-osteoclastogenesis in vitro and in vivo were assessed using RT-qPCR. Among the four major unsaturated fatty acids we tested, ALA displayed the strongest inhibitory effect on osteoclastogenesis. The increased expression of free fatty acid receptor 4 (FFAR4) and β-arrestin2 (βarr2), as well as the decreased expression of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), nuclear factor of activated T-cells c1 (NFATc1), and tartrate-resistant acid phosphatase (TRAP) in RAW264.7 cells after ALA treatment were observed. Moreover, in ovariectomized osteoporotic rats with ALA preventive intervention, we found that the expression of TNF-α, interleukin-6 (IL-6), interleukin-1β (IL-1β), NFATc1, and TRAP were decreased, while with the ALA therapeutic intervention, downregulated expression of NF-κB, NFATc1, TRAP, and transforming growth factor beta-activated kinase 1 (TAK1) were noticed. These results indicate that ALA, as the major unsaturated fatty acid in ZBSO, could inhibit RANKL-induced osteoclastogenesis via the FFAR4/βarr2 signaling pathway and could prevent inflammation, suggesting that ZBSO may be a promising potential natural product of unsaturated fatty acids and a dietary supplement for the prevention of osteoclastogenesis and inflammatory diseases. |
| first_indexed | 2024-03-11T09:44:01Z |
| format | Article |
| id | doaj.art-85b285307d5849adab51bbdba7c9f813 |
| institution | Directory Open Access Journal |
| issn | 2304-8158 |
| language | English |
| last_indexed | 2024-03-11T09:44:01Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Foods |
| spelling | doaj.art-85b285307d5849adab51bbdba7c9f8132023-11-16T16:42:50ZengMDPI AGFoods2304-81582023-02-0112368210.3390/foods12030682α-Linolenic Acid Inhibits RANKL-Induced Osteoclastogenesis In Vitro and Prevents Inflammation In VivoYufeng Deng0Weizhou Li1Yingying Zhang2Jingjing Li3Fangting He4Ke Dong5Zehui Hong6Ruocheng Luo7Xiaofang Pei8West China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu 610041, ChinaWest China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu 610041, ChinaWest China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu 610041, ChinaWest China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu 610041, ChinaWest China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu 610041, ChinaWest China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu 610041, ChinaWest China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu 610041, ChinaWest China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu 610041, ChinaWest China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu 610041, ChinaInflammation is an important risk factor for bone-destroying diseases. Our preliminary research found that <i>Zanthoxylum bungeanum</i> seed oil (ZBSO) is abundant in unsaturated fatty acids and could inhibit osteoclastogenesis in receptor activator of nuclear factor κB ligand (RANKL)-induced RAW264.7 cells. However, the key constituents in ZBSO in the prevention of osteoclastogenesis and its possible mechanism related to inflammation are still unclear. Therefore, in this study, oleic acid (OA), linoleic acid (LA), palmitoleic acid (PLA), and alpha-linolenic acid (ALA) in ZBSO, havingthe strongest effect on RANKL-induced osteoclastogenesis, were selected by a tartrate-resistant acid phosphatase (TRAP) staining method. Furthermore, the effects of the selected fatty acids on anti-inflammation and anti-osteoclastogenesis in vitro and in vivo were assessed using RT-qPCR. Among the four major unsaturated fatty acids we tested, ALA displayed the strongest inhibitory effect on osteoclastogenesis. The increased expression of free fatty acid receptor 4 (FFAR4) and β-arrestin2 (βarr2), as well as the decreased expression of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), nuclear factor of activated T-cells c1 (NFATc1), and tartrate-resistant acid phosphatase (TRAP) in RAW264.7 cells after ALA treatment were observed. Moreover, in ovariectomized osteoporotic rats with ALA preventive intervention, we found that the expression of TNF-α, interleukin-6 (IL-6), interleukin-1β (IL-1β), NFATc1, and TRAP were decreased, while with the ALA therapeutic intervention, downregulated expression of NF-κB, NFATc1, TRAP, and transforming growth factor beta-activated kinase 1 (TAK1) were noticed. These results indicate that ALA, as the major unsaturated fatty acid in ZBSO, could inhibit RANKL-induced osteoclastogenesis via the FFAR4/βarr2 signaling pathway and could prevent inflammation, suggesting that ZBSO may be a promising potential natural product of unsaturated fatty acids and a dietary supplement for the prevention of osteoclastogenesis and inflammatory diseases.https://www.mdpi.com/2304-8158/12/3/682alpha-linolenic acidosteoclastogenesisanti-inflammationovariectomized rat<i>Zanthoxylum bungeanum</i> seed oil |
| spellingShingle | Yufeng Deng Weizhou Li Yingying Zhang Jingjing Li Fangting He Ke Dong Zehui Hong Ruocheng Luo Xiaofang Pei α-Linolenic Acid Inhibits RANKL-Induced Osteoclastogenesis In Vitro and Prevents Inflammation In Vivo Foods alpha-linolenic acid osteoclastogenesis anti-inflammation ovariectomized rat <i>Zanthoxylum bungeanum</i> seed oil |
| title | α-Linolenic Acid Inhibits RANKL-Induced Osteoclastogenesis In Vitro and Prevents Inflammation In Vivo |
| title_full | α-Linolenic Acid Inhibits RANKL-Induced Osteoclastogenesis In Vitro and Prevents Inflammation In Vivo |
| title_fullStr | α-Linolenic Acid Inhibits RANKL-Induced Osteoclastogenesis In Vitro and Prevents Inflammation In Vivo |
| title_full_unstemmed | α-Linolenic Acid Inhibits RANKL-Induced Osteoclastogenesis In Vitro and Prevents Inflammation In Vivo |
| title_short | α-Linolenic Acid Inhibits RANKL-Induced Osteoclastogenesis In Vitro and Prevents Inflammation In Vivo |
| title_sort | α linolenic acid inhibits rankl induced osteoclastogenesis in vitro and prevents inflammation in vivo |
| topic | alpha-linolenic acid osteoclastogenesis anti-inflammation ovariectomized rat <i>Zanthoxylum bungeanum</i> seed oil |
| url | https://www.mdpi.com/2304-8158/12/3/682 |
| work_keys_str_mv | AT yufengdeng alinolenicacidinhibitsranklinducedosteoclastogenesisinvitroandpreventsinflammationinvivo AT weizhouli alinolenicacidinhibitsranklinducedosteoclastogenesisinvitroandpreventsinflammationinvivo AT yingyingzhang alinolenicacidinhibitsranklinducedosteoclastogenesisinvitroandpreventsinflammationinvivo AT jingjingli alinolenicacidinhibitsranklinducedosteoclastogenesisinvitroandpreventsinflammationinvivo AT fangtinghe alinolenicacidinhibitsranklinducedosteoclastogenesisinvitroandpreventsinflammationinvivo AT kedong alinolenicacidinhibitsranklinducedosteoclastogenesisinvitroandpreventsinflammationinvivo AT zehuihong alinolenicacidinhibitsranklinducedosteoclastogenesisinvitroandpreventsinflammationinvivo AT ruochengluo alinolenicacidinhibitsranklinducedosteoclastogenesisinvitroandpreventsinflammationinvivo AT xiaofangpei alinolenicacidinhibitsranklinducedosteoclastogenesisinvitroandpreventsinflammationinvivo |