PMID- 33610183
OWN - NLM
STAT- MEDLINE
DCOM- 20210824
LR  - 20210824
IS  - 1749-799X (Electronic)
IS  - 1749-799X (Linking)
VI  - 16
IP  - 1
DP  - 2021 Feb 20
TI  - Silymarin modulates catabolic cytokine expression through Sirt1 and SOX9 in human 
      articular chondrocytes.
PG  - 147
LID - 10.1186/s13018-021-02305-9 [doi]
LID - 147
AB  - 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-alpha) 
      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 muM) was 
      evaluated in human primary chondrocytes. The chondrocytes were supplemented with 
      SMN (25 and 50 muM) after interleukin-1beta (IL-1beta) 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 
      muM) impaired the mitochondrial activity in chondrocytes, and 50 muM SMN further 
      caused cell death in IL-1beta-stimulated cells. The addition of 25 muM SMN 
      ameliorated cell senescence; downregulated the catabolic genes of inducible 
      nitric oxide synthase, IL-1beta, TNF-alpha, 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-1beta, 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-1beta-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.
FAU - Wu, Wen-Tien
AU  - Wu WT
AD  - Department of Orthopedic Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi 
      Medical Foundation, No. 289, Jianguo Rd., Xindian Dist, New Taipei City, 23142, 
      Taiwan.
AD  - Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical 
      Foundation, Hualien, Taiwan.
AD  - Department of Orthopedics, School of Medicine, Tzu Chi University, Hualien, 
      Taiwan.
FAU - Chen, Yi-Ru
AU  - Chen YR
AD  - Department of Orthopedic Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi 
      Medical Foundation, No. 289, Jianguo Rd., Xindian Dist, New Taipei City, 23142, 
      Taiwan.
AD  - School of Dental Technology, College of Oral Medicine, Taipei Medical University, 
      No. 250, Wuxing St., Xinyi Dist, Taipei, 11031, Taiwan.
FAU - Lu, Dai-Hua
AU  - Lu DH
AD  - School of Dental Technology, College of Oral Medicine, Taipei Medical University, 
      No. 250, Wuxing St., Xinyi Dist, Taipei, 11031, Taiwan.
FAU - Senatov, Fedor Svyatoslavovich
AU  - Senatov FS
AD  - Researcher of the Centre for Composite Materials, National University of Science 
      and Technology MISIS, Moscow, Russia.
FAU - Yang, Kai-Chiang
AU  - Yang KC
AUID- ORCID: 0000-0002-0979-4463
AD  - Department of Orthopedic Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi 
      Medical Foundation, No. 289, Jianguo Rd., Xindian Dist, New Taipei City, 23142, 
      Taiwan. pumpkin@tmu.edu.tw.
AD  - School of Dental Technology, College of Oral Medicine, Taipei Medical University, 
      No. 250, Wuxing St., Xinyi Dist, Taipei, 11031, Taiwan. pumpkin@tmu.edu.tw.
FAU - Wang, Chen-Chie
AU  - Wang CC
AD  - Department of Orthopedic Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi 
      Medical Foundation, No. 289, Jianguo Rd., Xindian Dist, New Taipei City, 23142, 
      Taiwan. xaiver-wang@yahoo.com.tw.
AD  - Department of Orthopedics, School of Medicine, Tzu Chi University, Hualien, 
      Taiwan. xaiver-wang@yahoo.com.tw.
LA  - eng
GR  - IRB106-48-A/Buddhist Tzu Chi Medical Foundation/
PT  - Journal Article
DEP - 20210220
PL  - England
TA  - J Orthop Surg Res
JT  - Journal of orthopaedic surgery and research
JID - 101265112
RN  - 0 (Cytokines)
RN  - 0 (SOX9 Transcription Factor)
RN  - 0 (SOX9 protein, human)
RN  - 0 (Silymarin)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Cartilage, Articular/*drug effects
MH  - Chondrocytes/*drug effects
MH  - Cytokines/*metabolism
MH  - Down-Regulation
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Osteoarthritis, Knee/drug therapy
MH  - SOX9 Transcription Factor/*metabolism
MH  - Silymarin/*pharmacology
MH  - Sirtuin 1/*metabolism
MH  - Up-Regulation
PMC - PMC7896383
OTO - NOTNLM
OT  - Catabolic cytokine
OT  - Matrix metalloproteinase
OT  - Osteoarthritis
OT  - Silymarin
OT  - Sirtuin-1
COIS- The authors declare that they have no competing interests.
EDAT- 2021/02/22 06:00
MHDA- 2021/08/25 06:00
PMCR- 2021/02/20
CRDT- 2021/02/21 20:23
PHST- 2020/11/29 00:00 [received]
PHST- 2021/02/15 00:00 [accepted]
PHST- 2021/02/21 20:23 [entrez]
PHST- 2021/02/22 06:00 [pubmed]
PHST- 2021/08/25 06:00 [medline]
PHST- 2021/02/20 00:00 [pmc-release]
AID - 10.1186/s13018-021-02305-9 [pii]
AID - 2305 [pii]
AID - 10.1186/s13018-021-02305-9 [doi]
PST - epublish
SO  - J Orthop Surg Res. 2021 Feb 20;16(1):147. doi: 10.1186/s13018-021-02305-9.