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Int. J. Mol. Sci. 2016, 17(5), 730; doi:10.3390/ijms17050730

Pigment Epithelium-Derived Factor (PEDF) Protects Osteoblastic Cell Line from Glucocorticoid-Induced Apoptosis via PEDF-R

1
Department of Orthopaedic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China
2
Department of Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China
3
Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China
4
Research Facility Center for Morphology, Xuzhou Medical University, Xuzhou 221004, China
*
Author to whom correspondence should be addressed.
Academic Editor: Charles J. Malemud
Received: 11 March 2016 / Revised: 28 April 2016 / Accepted: 6 May 2016 / Published: 13 May 2016
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Pigment epithelial-derived factor (PEDF) is known as a widely expressed multifunctional secreted glycoprotein whose biological actions are cell-type dependent. Recent studies demonstrated that PEDF displays cytoprotective activity in several cell types. However, it remains unknown whether PEDF is involved in glucocorticoid-induced osteoblast death. The aim of this study was to examine the role of PEDF in osteoblast survival in response to dexamethasone, an active glucocorticoid analogue, and explore the underlying mechanism. In the present study, dexamethasone (DEX) was used to induce MC3T3-E1 pre-osteoblast apoptosis. PEDF mRNA and protein levels and cell apoptosis were determined respectively. Then PEDF receptor (PEDF-R)- and lysophosphatidic acid (LPA)-related signal transductions were assessed. Here we show that DEX down-regulates PEDF expression, which contributes to osteoblast apoptosis. As a result, exogenous recombinant PEDF (rPEDF) inhibited DEX-induced cell apoptosis. We confirmed that PEDF-R was expressed on MC3T3-E1 pre-osteoblast membrane and could bind to PEDF which increased the level of LPA and activated the phosphorylation of Akt. Our results suggest that PEDF attenuated DEX-induced apoptosis in MC3T3-E1 pre-osteoblasts through LPA-dependent Akt activation via PEDF-R. View Full-Text
Keywords: pigment epithelium-derived factor; glucocorticoids; apoptosis; pigment epithelium-derived factor receptor; lysophosphatidic acid; PI3K/Akt signaling pigment epithelium-derived factor; glucocorticoids; apoptosis; pigment epithelium-derived factor receptor; lysophosphatidic acid; PI3K/Akt signaling
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Yao, S.; Zhang, Y.; Wang, X.; Zhao, F.; Sun, M.; Zheng, X.; Dong, H.; Guo, K. Pigment Epithelium-Derived Factor (PEDF) Protects Osteoblastic Cell Line from Glucocorticoid-Induced Apoptosis via PEDF-R. Int. J. Mol. Sci. 2016, 17, 730.

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