Document Detail


Bovine lactoferricin induces TIMP-3 via the ERK1/2-Sp1 axis in human articular chondrocytes.
MedLine Citation:
PMID:  23313877     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bovine lactoferricin (LfcinB) is a heparan sulfate-binding peptide with multiple bioactivities. In human articular cartilage, LfcinB antagonizes interleukin-1 β (IL-1β) and fibroblast growth factor 2 (FGF-2) in proteoglycan metabolism, catabolic protease expression, and induction of pro-inflammatory mediators. LfcinB specifically activates ERK1/2, p38 and Akt, but whether these signaling pathways control the expression of LfcinB target genes remained unknown. In this report, we characterized a novel aspect of LfcinB-mediated genetic response in human articular chondrocytes, tissue inhibitor of metalloproteinase 3 (TIMP-3) induction. Inhibition of individual signaling pathways revealed that ERK1/2 functions as the major pathway in TIMP-3 expression, whereas Akt plays a minor role. Further investigation identified Sp1 as a critical transcriptional activator in TIMP-3 regulation, and Sp1 activity is modulated by ERK1/2, not Akt. Comparative quantification indicates that significant downregulation of TIMP-3 occurs in OA chondrocytes, suggesting a beneficial role of LfcinB in OA pathogenesis. Our results collectively provide new insights into the mechanism of action of LfcinB, and support the candidacy of LfcinB as a chondroprotective agent.
Authors:
Dongyao Yan; Di Chen; John R Hawse; Andre J van Wijnen; Hee-Jeong Im
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-11
Journal Detail:
Title:  Gene     Volume:  517     ISSN:  1879-0038     ISO Abbreviation:  Gene     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-12     Completed Date:  2013-04-16     Revised Date:  2014-07-14    
Medline Journal Info:
Nlm Unique ID:  7706761     Medline TA:  Gene     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  12-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Animals
Anti-Bacterial Agents / pharmacology
Blotting, Western
Cartilage, Articular / metabolism*,  pathology
Case-Control Studies
Cattle
Cells, Cultured
Chondrocytes / metabolism*,  pathology
Electrophoretic Mobility Shift Assay
Humans
Immunoenzyme Techniques
Lactoferrin / pharmacology*
Middle Aged
Mitogen-Activated Protein Kinase 1 / genetics,  metabolism*
Mitogen-Activated Protein Kinase 3 / genetics,  metabolism*
Osteoarthritis / genetics,  metabolism*,  pathology
Promoter Regions, Genetic / genetics
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Sp1 Transcription Factor / genetics,  metabolism*
Tissue Inhibitor of Metalloproteinase-3 / genetics*,  metabolism
Grant Support
ID/Acronym/Agency:
AR053220/AR/NIAMS NIH HHS; AR062136/AR/NIAMS NIH HHS; DE014036/DE/NIDCR NIH HHS; R01 AR049069/AR/NIAMS NIH HHS; R01 AR053220/AR/NIAMS NIH HHS; R01 AR054465/AR/NIAMS NIH HHS; R01 AR055915/AR/NIAMS NIH HHS; R01 AR062136/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/RNA, Messenger; 0/Sp1 Transcription Factor; 0/TIMP3 protein, human; 0/Tissue Inhibitor of Metalloproteinase-3; 146897-68-9/lactoferricin B; EC 2.7.11.24/MAPK1 protein, human; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 3.4.21.-/Lactoferrin
Comments/Corrections

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