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A novel FGFR1-binding peptide attenuates the degeneration ofarticular cartilage in adult mice
Q. Tan1; B. Chen1; Q. Wang1; W.Xu1; Y.Wang2; Z. Lin2; F.Luo1; S. Huang1; Y.Zhu1; N. Su1; M. Jin1; C.Li1; L. Kuang1; H.Qi1; Z.Ni1; Z. Wang1; X. Luo1; W. Jiang1; H. Chen1; S. Chen1; F.Li1; B. Zhang1; J. Huang1; R. Zhang1; K. Jin1; X.Xu3; C. Deng3; X.Du1; Y. Xie1; L. Chen1
2018-12
Source PublicationOsteoarthritis and Cartilage
ISSN1063-4584
Volume26Issue:12Pages:1733-1743
Other Abstract

Objective

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 Peptide Osteoarthritis Mice
DOIhttps://doi.org/10.1016/j.joca.2018.08.012
Indexed BySCI
Language英语
WOS Research AreaOrthopedics ; Rheumatology
WOS SubjectOrthopedics ; Rheumatology
WOS IDWOS:000451049900021
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Co-First AuthorQ. Tan
Corresponding AuthorX.Du; Y. Xie; L. Chen
Affiliation1.Department of Rehabilitation Medicine, Laboratory for the Rehabilitation of Traumatic Injuries, State Key Laboratory of Trauma, Burns and CombinedInjury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chon
2.College of Bioengineering, Chongqing Institute of Technology, Chongqing 400050, China
3.Faculty of Health Sciences, University of Macau, Macau SAR 00853, China
Recommended Citation
GB/T 7714
Q. Tan,B. Chen,Q. Wang,et al. A novel FGFR1-binding peptide attenuates the degeneration ofarticular cartilage in adult mice[J]. Osteoarthritis and Cartilage,2018,26(12):1733-1743.
APA Q. Tan.,B. Chen.,Q. Wang.,W.Xu.,Y.Wang.,...&L. Chen.(2018).A novel FGFR1-binding peptide attenuates the degeneration ofarticular cartilage in adult mice.Osteoarthritis and Cartilage,26(12),1733-1743.
MLA Q. Tan,et al."A novel FGFR1-binding peptide attenuates the degeneration ofarticular cartilage in adult mice".Osteoarthritis and Cartilage 26.12(2018):1733-1743.
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