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Osthole Inhibits Proliferation and Induces Catabolism in Rat Chondrocytes and Cartilage Tissue
- Source :
- Cellular Physiology and Biochemistry, Vol 36, Iss 6, Pp 2480-2493 (2015)
- Publication Year :
- 2015
-
Abstract
- Background/Aims: Cartilage destruction is thought to be the major mediator of osteoarthritis. Recent studies suggest that inhibition of subchrondral bone loss by anti-osteoporosis (OP) drug can protect cartilige erosion. Osthole, as a promising agent for treating osteoporosis, may show potential in treating osteoarthritis. The purpose of this study was to investigate whether Osthole affects the proliferation and catabolism of rat chondrocytes, and the degeneration of cartilage explants. Methods: Rat chondrocytes were treated with Osthole (0 μM, 6.25 μM, 12.5 μM, and 25 μM) with or without IL1-β (10ng/ml) for 24 hours. The expression levels of type II collagen and MMP13 were detected by western Blot. Marker genes for chondrocytes (A-can and Sox9), matrix metalloproteinases (MMPs), aggrecanases (ADAMTS5) and genes implicated in extracellular matrix catabolism were evaluated by qPCR. Cell proliferation was assessed by measuring proliferating cell nuclear antigen (PCNA) expression and fluorescence activated cell sorter. Wnt7b/β-catenin signaling was also investigated. Cartilage explants from two-week old SD rats were cultured with IL-1β, Osthole and Osthole plus IL-1β for four days and glycosaminoglycan (GAG) synthesis was assessed with toluidine blue staining and Safranine O/Fast Green FCF staining, collagen type II expression was detected by immunofuorescence. Results: Osthole reduced expression of chondrocyte markers and increased expression of MMP13, ADAMTS5 and MMP9 in a dose-dependent manner. Catabolic gene expression levels were further improved by Osthole plus IL-1β. Osthole inhibited chondrocyte proliferation. GAG synthesis and type II collagen were decreased in both the IL-1β groups and the Osthole groups, and significantly reduced by Osthole plus IL-1β. Conclusions: Our data suggested that Osthole increases the catabolism of rat chondrocytes and cartilage explants, this effect might be mediated through inhibiting Wnt7b/β-catenin pathway.
- Subjects :
- Cartilage, Articular
Physiology
Proliferation
Interleukin-1beta
Type II collagen
MMP9
Matrix metalloproteinase
lcsh:Physiology
Chondrocyte
lcsh:Biochemistry
Extracellular matrix
Glycosaminoglycan
Rats, Sprague-Dawley
Chondrocytes
Coumarins
medicine
Animals
Cartilage tissue
lcsh:QD415-436
RNA, Messenger
Wnt Signaling Pathway
Cells, Cultured
Cell Proliferation
Glycosaminoglycans
lcsh:QP1-981
Catabolism
Chemistry
Cartilage
Osthole
Molecular biology
Matrix Metalloproteinases
Extracellular Matrix
ADAM Proteins
medicine.anatomical_structure
Biochemistry
Gene Expression Regulation
ADAMTS5 Protein
Biomarkers
Subjects
Details
- ISSN :
- 14219778
- Volume :
- 36
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
- Accession number :
- edsair.doi.dedup.....1fc77c0db6b1762d99693e734df0b886