UM
A novel FGFR1-binding peptide attenuates the degeneration of articular cartilage in adult mice
Tan Q.1; Chen B.1; Wang Q.1; Xu W.1; Wang Y.2; Lin Z.2; Luo F.1; Huang S.1; Zhu Y.1; Su N.1; Jin M.1; Li C.1; Kuang L.1; Qi H.1; Ni Z.1; Wang Z.1; Luo X.1; Jiang W.1; Chen H.1; Chen S.1; Li F.1; Zhang B.1; Huang J.1; Zhang R.1; Jin K.1; Xu X.3; Deng C.3; Du X.1; Xie Y.1; Chen L.1
2018-12-01
Source PublicationOsteoarthritis and Cartilage
ISSN15229653 10634584
Volume26Issue:12Pages:1733-1743
AbstractObjective: We previously reported that genetic ablation of (Fibroblast Growth Factors Receptors) FGFR1 in knee cartilage attenuates the degeneration of articular cartilage in adult mice, which suggests that FGFR1 is a potential targeting molecule for osteoarthritis (OA). Here, we identified R1-P1, an inhibitory peptide for FGFR1 and investigated its effect on the pathogenesis of OA in mice induced by destabilization of medial meniscus (DMM). Design: Binding ability between R1-P1 and FGFR1 protein was evaluated by enzyme-linked immuno sorbent assay (ELISA) and molecular docking. Alterations in cartilage were evaluated histologically. The expression levels of molecules associated with articular cartilage homeostasis and FGFR1 signaling were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC). The chondrocyte apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. Results: R1-P1 had highly binding affinities to human FGFR1 protein, and efficiently inhibited extracellular signal-regulated kinase (ERK)1/2 pathway in mouse primary chondrocytes. In addition, R1-P1 attenuated the IL-1β induced significant loss of proteoglycan in full-thickness cartilage tissue from human femur head. Moreover, this peptide can significantly restore the IL-1β mediated loss of proteoglycan and type II collagen (Col II) and attenuate the expression of matrix metalloproteinase-13 (MMP13) in mouse primary chondrocytes. Finally, intra-articular injection of R1-P1 remarkably attenuated the loss of proteoglycan and the destruction of articular cartilage and decreased the expressions of extracellular matrix (ECM) degrading enzymes and apoptosis in articular chondrocytes of mice underwent DMM surgery. Conclusions: R1-P1, a novel inhibitory peptide for FGFR1, attenuates the degeneration of articular cartilage in adult mice, which is a potential leading molecule for the treatment of OA.
KeywordFGFR1 Mice Osteoarthritis Peptide
DOI10.1016/j.joca.2018.08.012
URLView the original
Indexed BySCI
Language英語
WOS Research AreaOrthopedics ; Rheumatology
WOS SubjectOrthopedics ; Rheumatology
WOS IDWOS:000451049900021
PublisherELSEVIER SCI LTD
Fulltext Access
Citation statistics
Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Personal research not belonging to the institution
Affiliation1.Daping Hospital, the Third Military Medical University
2.Chongqing University of Technology
3.Universidade de Macau
Recommended Citation
GB/T 7714
Tan Q.,Chen B.,Wang Q.,et al. A novel FGFR1-binding peptide attenuates the degeneration of articular cartilage in adult mice[J]. Osteoarthritis and Cartilage,2018,26(12):1733-1743.
APA Tan Q..,Chen B..,Wang Q..,Xu W..,Wang Y..,...&Chen L..(2018).A novel FGFR1-binding peptide attenuates the degeneration of articular cartilage in adult mice.Osteoarthritis and Cartilage,26(12),1733-1743.
MLA Tan Q.,et al."A novel FGFR1-binding peptide attenuates the degeneration of articular cartilage in adult mice".Osteoarthritis and Cartilage 26.12(2018):1733-1743.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Tan Q.]'s Articles
[Chen B.]'s Articles
[Wang Q.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Tan Q.]'s Articles
[Chen B.]'s Articles
[Wang Q.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Tan Q.]'s Articles
[Chen B.]'s Articles
[Wang Q.]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.