Artesunate, an Anti-Malaria Agent, Attenuates Experimental Osteoarthritis by Inhibiting Bone Resorption and CD31hiEmcnhi Vessel Formation in Subchondral Bone
Osteoarthritis (OA) is a common and debilitating joint disease worldwide without interventions available to reverse its progression. Artesunate (ART), an anti-malaria agent, possesses diverse biological activities, including the inhibition of osteoclastogenesis and angiogenesis in various cells, but its role in subchondral bone during OA progression is not known. Here, we explored the curative effects of ART on the pathogenesis of OA in anterior cruciate ligament transection (ACLT) mice models. We found that ART attenuated articular cartilage degeneration, defined by lowered histologic scoring of OA and retarded calcification of the cartilage zone. Moreover, ART improved the expression of lubricin and aggrecan and reduced the expression of collagen X (Col X) and matrix metalloproteinase-13 (MMP-13). In parallel, ART normalized abnormal subchondral bone remodeling by maintaining bone volume fraction (BV/TV) and subchondral bone plate thickness (SBP Th) and reducing trabecular pattern factor (Tb.pf) compared to the vehicle-treated mice. Our results indicated that ART suppressed osteoclastic bone resorption through regulating RANKL-OPG system, restored coupled bone remodeling by indirectly inhibiting TGF-β/Smad2/3 signaling. Additionally, ART abrogated CD31hiEmcnhi vessel formation via downregulating the expression of vascular endothelial growth factor (VEGF) and angiogenin-1 in subchondral bone. In conclusion, ART attenuates ACLT-induced OA by blocking bone resorption and CD31hiEmcnhi vessel formation in subchondral bone, indicating that this may be a new therapeutic alternative for OA.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Frontiers in pharmacology - 10(2019) vom: 28., Seite 685 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Yicheng [VerfasserIn] |
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| Links: |
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| Themen: |
Artesunate |
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| Anmerkungen: |
Date Revised 01.10.2020 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fphar.2019.00685 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a Osteoarthritis (OA) is a common and debilitating joint disease worldwide without interventions available to reverse its progression. Artesunate (ART), an anti-malaria agent, possesses diverse biological activities, including the inhibition of osteoclastogenesis and angiogenesis in various cells, but its role in subchondral bone during OA progression is not known. Here, we explored the curative effects of ART on the pathogenesis of OA in anterior cruciate ligament transection (ACLT) mice models. We found that ART attenuated articular cartilage degeneration, defined by lowered histologic scoring of OA and retarded calcification of the cartilage zone. Moreover, ART improved the expression of lubricin and aggrecan and reduced the expression of collagen X (Col X) and matrix metalloproteinase-13 (MMP-13). In parallel, ART normalized abnormal subchondral bone remodeling by maintaining bone volume fraction (BV/TV) and subchondral bone plate thickness (SBP Th) and reducing trabecular pattern factor (Tb.pf) compared to the vehicle-treated mice. Our results indicated that ART suppressed osteoclastic bone resorption through regulating RANKL-OPG system, restored coupled bone remodeling by indirectly inhibiting TGF-β/Smad2/3 signaling. Additionally, ART abrogated CD31hiEmcnhi vessel formation via downregulating the expression of vascular endothelial growth factor (VEGF) and angiogenin-1 in subchondral bone. In conclusion, ART attenuates ACLT-induced OA by blocking bone resorption and CD31hiEmcnhi vessel formation in subchondral bone, indicating that this may be a new therapeutic alternative for OA | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CD31hiEmcnhi vessel formation | |
| 650 | 4 | |a artesunate | |
| 650 | 4 | |a bone resorption | |
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| 700 | 1 | |a Xu, Boyong |e verfasserin |4 aut | |
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| 700 | 1 | |a Wahafu, Tuerhongjiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wuermanbieke, Shalitanati |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Hairong |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Hongwei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Keyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Amat, Abdusami |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Li |e verfasserin |4 aut | |
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