title: Pigment Epithelium-Derived Factor (PEDF) Protects Osteoblastic Cell Line from Glucocorticoid-Induced Apoptosis via PEDF-R.
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.
authors.affiliation: Department of Orthopaedic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China. surgeony@126.com.
authors.forename: Shengcheng
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China. zyn_xzmc@163.com.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China. wxy_xzmc@163.com.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China. Zhjianzh@sina.com.
authors.forename: Fengchao
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China. holycityy@126.com.
authors.forename: Maji
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Orthopaedic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China. thindy1980@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Research Facility Center for Morphology, Xuzhou Medical University, Xuzhou 221004, China. dhy@xzmc.edu.cn.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Orthopaedic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China. kj_guoxzmc@163.com.
authors.forename: Kaijin
authors.initials: K
authors.lastname: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D003907:Dexamethasone / Q000633:toxicity; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D003907:Dexamethasone; D005136:Eye Proteins; D009414:Nerve Growth Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018013:Receptors, Neuropeptide; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C400531:pigment epithelium-derived factor receptor
keywords: PI3K/Akt signaling; apoptosis; glucocorticoids; lysophosphatidic acid; pigment epithelium-derived factor; pigment epithelium-derived factor receptor