Lovastatin impairs cellular proliferation and enhances hyaluronic acid production in fibroblast-like synoviocytes
Copyright © 2023. Published by Elsevier Ltd..
INTRODUCTION: Statins have demonstrated chondroprotective effects by reducing inflammation and mitigating extracellular matrix degradation. However, statins are also reported to be cytotoxic to several types of cells. Early-onset osteoarthritis (OA) is characterized by synovial inflammation, which adversely affects hyaluronan (HA) production in fibroblast-like synoviocytes (FLSs). Nevertheless, the precise effects of statins on the synovium remain unclear.
METHODS: This study investigated the impact of lovastatin on human FLSs, and HA secretion-related genes, signaling pathways, and production were evaluated.
RESULTS: The findings revealed that high doses of lovastatin (20 or 40 μM) decreased FLS viability and increased cell death. FLS proliferation ceased when cultured in a medium containing 5 or 10 μM lovastatin. mRNA expression analysis demonstrated that lovastatin (5 and 10 μM) upregulated the gene level of hyaluronan synthase 1 (HAS1), HAS2, and proteoglycan 4 (PRG4), but not HAS3. While the expression of multidrug resistance-associated protein 5 transporter gene remained unaffected, both inward-rectifying potassium channel and acid-sensing ion channel 3 were upregulated. Western blot further confirmed that lovastatin increased the production of HAS1 and PRG4, and activated the PKC-α, ERK1/2, and p38-MAPK signaling pathways. Additionally, lovastatin elevated intracellular cAMP levels and HA production in FLSs.
CONCLUSION: Lovastatin impairs cellular proliferation but enhances HA production in human FLSs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:97 |
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| Enthalten in: |
Toxicology in vitro : an international journal published in association with BIBRA - 97(2024) vom: 20. Apr., Seite 105806 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Wen-Tien [VerfasserIn] |
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| Links: |
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| Themen: |
9004-61-9 |
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| Anmerkungen: |
Date Completed 16.04.2024 Date Revised 16.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.tiv.2024.105806 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM369224477 |
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| 500 | |a Date Revised 16.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023. Published by Elsevier Ltd. | ||
| 520 | |a INTRODUCTION: Statins have demonstrated chondroprotective effects by reducing inflammation and mitigating extracellular matrix degradation. However, statins are also reported to be cytotoxic to several types of cells. Early-onset osteoarthritis (OA) is characterized by synovial inflammation, which adversely affects hyaluronan (HA) production in fibroblast-like synoviocytes (FLSs). Nevertheless, the precise effects of statins on the synovium remain unclear | ||
| 520 | |a METHODS: This study investigated the impact of lovastatin on human FLSs, and HA secretion-related genes, signaling pathways, and production were evaluated | ||
| 520 | |a RESULTS: The findings revealed that high doses of lovastatin (20 or 40 μM) decreased FLS viability and increased cell death. FLS proliferation ceased when cultured in a medium containing 5 or 10 μM lovastatin. mRNA expression analysis demonstrated that lovastatin (5 and 10 μM) upregulated the gene level of hyaluronan synthase 1 (HAS1), HAS2, and proteoglycan 4 (PRG4), but not HAS3. While the expression of multidrug resistance-associated protein 5 transporter gene remained unaffected, both inward-rectifying potassium channel and acid-sensing ion channel 3 were upregulated. Western blot further confirmed that lovastatin increased the production of HAS1 and PRG4, and activated the PKC-α, ERK1/2, and p38-MAPK signaling pathways. Additionally, lovastatin elevated intracellular cAMP levels and HA production in FLSs | ||
| 520 | |a CONCLUSION: Lovastatin impairs cellular proliferation but enhances HA production in human FLSs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cellular proliferation | |
| 650 | 4 | |a Fibroblast-like synoviocyte | |
| 650 | 4 | |a Hyaluronan synthase | |
| 650 | 4 | |a Statin | |
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| 700 | 1 | |a Lu, Dai-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Kuan-Jung |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Yu-Chia |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Kai-Chiang |e verfasserin |4 aut | |
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