L-arginine metabolism inhibits arthritis and inflammatory bone loss
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
OBJECTIVES: To investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss.
METHODS: L-arginine was applied to three arthritis models (collagen-induced arthritis, serum-induced arthritis and human TNF transgenic mice). Inflammation was assessed clinically and histologically, while bone changes were quantified by μCT and histomorphometry. In vitro, effects of L-arginine on osteoclast differentiation were analysed by RNA-seq and mass spectrometry (MS). Seahorse, Single Cell ENergetIc metabolism by profilIng Translation inHibition and transmission electron microscopy were used for detecting metabolic changes in osteoclasts. Moreover, arginine-associated metabolites were measured in the serum of rheumatoid arthritis (RA) and pre-RA patients.
RESULTS: L-arginine inhibited arthritis and bone loss in all three models and directly blocked TNFα-induced murine and human osteoclastogenesis. RNA-seq and MS analyses indicated that L-arginine switched glycolysis to oxidative phosphorylation in inflammatory osteoclasts leading to increased ATP production, purine metabolism and elevated inosine and hypoxanthine levels. Adenosine deaminase inhibitors blocking inosine and hypoxanthine production abolished the inhibition of L-arginine on osteoclastogenesis in vitro and in vivo. Altered arginine levels were also found in RA and pre-RA patients.
CONCLUSION: Our study demonstrated that L-arginine ameliorates arthritis and bone erosion through metabolic reprogramming and perturbation of purine metabolism in osteoclasts.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:83 |
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| Enthalten in: |
Annals of the rheumatic diseases - 83(2024), 1 vom: 02. Jan., Seite 72-87 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cao, Shan [VerfasserIn] |
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| Links: |
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| Themen: |
5A614L51CT |
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| Anmerkungen: |
Date Completed 04.01.2024 Date Revised 25.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1136/ard-2022-223626 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362712336 |
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| 245 | 1 | 0 | |a L-arginine metabolism inhibits arthritis and inflammatory bone loss |
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| 500 | |a Date Completed 04.01.2024 | ||
| 500 | |a Date Revised 25.01.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a OBJECTIVES: To investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss | ||
| 520 | |a METHODS: L-arginine was applied to three arthritis models (collagen-induced arthritis, serum-induced arthritis and human TNF transgenic mice). Inflammation was assessed clinically and histologically, while bone changes were quantified by μCT and histomorphometry. In vitro, effects of L-arginine on osteoclast differentiation were analysed by RNA-seq and mass spectrometry (MS). Seahorse, Single Cell ENergetIc metabolism by profilIng Translation inHibition and transmission electron microscopy were used for detecting metabolic changes in osteoclasts. Moreover, arginine-associated metabolites were measured in the serum of rheumatoid arthritis (RA) and pre-RA patients | ||
| 520 | |a RESULTS: L-arginine inhibited arthritis and bone loss in all three models and directly blocked TNFα-induced murine and human osteoclastogenesis. RNA-seq and MS analyses indicated that L-arginine switched glycolysis to oxidative phosphorylation in inflammatory osteoclasts leading to increased ATP production, purine metabolism and elevated inosine and hypoxanthine levels. Adenosine deaminase inhibitors blocking inosine and hypoxanthine production abolished the inhibition of L-arginine on osteoclastogenesis in vitro and in vivo. Altered arginine levels were also found in RA and pre-RA patients | ||
| 520 | |a CONCLUSION: Our study demonstrated that L-arginine ameliorates arthritis and bone erosion through metabolic reprogramming and perturbation of purine metabolism in osteoclasts | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Arthritis | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Osteoporosis | |
| 650 | 7 | |a Arginine |2 NLM | |
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| 700 | 1 | |a Li, Yixuan |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Xianyi |e verfasserin |4 aut | |
| 700 | 1 | |a Fuchs, Maximilian |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Chunguang |e verfasserin |4 aut | |
| 700 | 1 | |a Kachler, Katerina |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Xinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Jinming |e verfasserin |4 aut | |
| 700 | 1 | |a Schlötzer-Schrehardt, Ursula |e verfasserin |4 aut | |
| 700 | 1 | |a Taudte, Verena |e verfasserin |4 aut | |
| 700 | 1 | |a Gessner, Arne |e verfasserin |4 aut | |
| 700 | 1 | |a Kunz, Meik |e verfasserin |4 aut | |
| 700 | 1 | |a Schleicher, Ulrike |e verfasserin |4 aut | |
| 700 | 1 | |a Zaiss, Mario M |e verfasserin |4 aut | |
| 700 | 1 | |a Kastbom, Alf |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiaoxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Schett, Georg |e verfasserin |4 aut | |
| 700 | 1 | |a Bozec, Aline |e verfasserin |4 aut | |
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