NDLI: Pigment Epithelium-Derived Factor (PEDF) mediates cartilage matrix loss in an age-dependent manner under inflammatory conditions

Content Provider	Springer Nature : BioMed Central
Author	Nakamura, Daisy S. Hollander, Judith M. Uchimura, Tomoya Nielsen, Heber C. Zeng, Li
Abstract	Background Inflammation is a major cause of cartilage destruction and leads to the imbalance of metabolic activities in the arthritic joint. Pigment epithelium-derived factor (PEDF) has been reported to have both pro- and anti-inflammatory activities in various cell types and to be upregulated in the arthritic joint, but its role in joint destruction is unclear. Our aim was to investigate the role of PEDF in cartilage degeneration under inflammatory conditions. Methods PEDF was ectopically expressed in primary human articular chondrocytes, and catabolic gene expression and protein secretion in response to the pro-inflammatory cytokine interleukin 1 beta (IL-1β) were evaluated. Metatarsal bones from PEDF-deficient and wild type mice were cultured in the presence or absence of IL-1β. Cartilage matrix integrity and matrix metalloproteinases MMP-1, MMP-3, and MMP-13 were evaluated. PEDF-deficient and wild type mice were evaluated in the monosodium iodoacetate (MIA) inflammatory joint destruction animal model to determine the role of PEDF in inflammatory arthritis in vivo. Student’s t-tests and Mann–Whitney tests were employed where appropriate, for parametric and non-parametric data, respectively. Results We showed that PEDF protein levels were higher in human osteoarthritis samples compared to normal samples. We demonstrated that ectopic PEDF expression in primary human articular chondrocytes exacerbated catabolic gene expression in the presence of IL-1β. In whole bone organ cultures, IL-1β induced MMP-1, MMP-3 and MMP-13 protein production, and caused significant cartilage matrix loss. Interestingly, Toluidine Blue staining showed that PEDF-deficient bones from 29 week old animals, but not 10 week old animals, had reduced matrix loss in response to IL-1β compared to their wild type counterparts. In addition, PEDF-deficiency in 29 week old animals preserved matrix integrity and protected against cell loss in the MIA joint destruction model in vivo. Conclusion We conclude that PEDF exacerbates cartilage degeneration in an age-dependent manner under an inflammatory setting. This is the first study identifying a specific role for PEDF in joint inflammation and highlights the multi-faceted activities of PEDF.
Related Links	https://bmcmusculoskeletdisord.biomedcentral.com/counter/pdf/10.1186/s12891-017-1410-y.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
ISSN	14712474
DOI	10.1186/s12891-017-1410-y
Journal	BMC Musculoskeletal Disorders
Issue Number	1
Volume Number	18
Language	English
Publisher	BioMed Central
Publisher Date	2017-01-25
Access Restriction	Open
Subject Keyword	Orthopedics Rehabilitation Rheumatology Sports Medicine Internal Medicine Epidemiology Pigment epithelium-derived factor Matrix cartilage IL-1β MMPs Arthritis Inflammation SERPINF1 Age-related
Content Type	Text
Resource Type	Article
Subject	Orthopedics and Sports Medicine Rheumatology
Journal Impact Factor	2.2/2023
5-Year Journal Impact Factor	2.6/2023

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