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Silymarin modulates catabolic cytokine expression through Sirt1 and SOX9 in human articular chondrocytes.
- Source :
-
Journal of Orthopaedic Surgery & Research . 2/20/2021, Vol. 16 Issue 1, p1-9. 9p. - Publication Year :
- 2021
-
Abstract
- Background: Silymarin (SMN), a polyphenolic flavonoid, is involved in multiple bioactive functions including anti-inflammation. Pretreatment with SMN demonstrated chondroprotection against tumour necrosis factor-alpha (TNF-α) stimulation in a chondrocyte cell line. However, pre- and posttreatment with phytochemicals have varying effects on osteoarthritis (OA) chondrocytes, and the therapeutic potential of SMN after catabolic cytokine stimulation is not fully elucidated. Methods: The cytotoxicity of SMN (12.5, 25, 50 and 100 μM) was evaluated in human primary chondrocytes. The chondrocytes were supplemented with SMN (25 and 50 μM) after interleukin-1beta (IL-1β) stimulation. The mRNA expression and protein production of catabolic/anabolic cytokines as well as extracellular matrix (ECM) components were evaluated. Results: High-dose SMN (100 μM) impaired the mitochondrial activity in chondrocytes, and 50 μM SMN further caused cell death in IL-1β-stimulated cells. The addition of 25 μM SMN ameliorated cell senescence; downregulated the catabolic genes of inducible nitric oxide synthase, IL-1β, TNF-α, matrix metalloproteinase-3 (MMP-3), MMP-9 and MMP-13; upregulated the anabolic genes of tissue inhibitor of metalloproteinase-1 (TIMP-1) and collagen type II alpha 1; and restored the expression of chondrogenic phenotype genes SOX9 and sirtuin-1 (Sirt1). In addition, the production of IL-1β, MMP-3 and MMP-9 decreased with an increase in TIMP-1 secretion. However, the mRNA levels of IL-6, IL-8 and IL-10 and protein production remained high. The addition of nicotinamide, a Sirt1 inhibitor, downregulated SOX9 and attenuated the therapeutic effects of SMN on IL-1β-stimulated chondrocytes. Conclusion: SMN regulates the chondrocyte phenotype through Sirt1 and SOX9 to improve ECM homeostasis and may serve as a complementary therapy for early-stage knee OA. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CYTOKINES
*CARTILAGE cells
*COLLAGEN
*FLAVONOIDS
*CLINICAL trials
*METABOLISM
*INTERLEUKIN-1
*DRUG-food interactions
*GENE expression
*TREATMENT effectiveness
*MITOCHONDRIA
*MATRIX metalloproteinases
*VITAMIN B complex
*OSTEOARTHRITIS
*MESSENGER RNA
*TUMOR necrosis factors
*ARTICULAR cartilage
*EXTRACELLULAR space
*OXIDOREDUCTASES
*CELL death
*PHENOTYPES
*EVALUATION
Subjects
Details
- Language :
- English
- ISSN :
- 1749799X
- Volume :
- 16
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Orthopaedic Surgery & Research
- Publication Type :
- Academic Journal
- Accession number :
- 148903828
- Full Text :
- https://doi.org/10.1186/s13018-021-02305-9