{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:42:36Z","timestamp":1791330156983,"version":"4.3.1"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pigment epithelium-derived factor (PEDF) is a potent antiangiogenic factor found in a wide variety of tissues. Recent findings indicated that lack of PEDF leads to osteogenesis imperfecta type VI whose hallmark is a defect in mineralization. We investigated the effects of PEDF on human mesenchymal stem cells (hMSCs) and signaling pathways through which PEDF displays its activities in hMSCs. hMSCs incubated in a medium supplemented with PEDF induced expression of osteoblastic-related genes. In addition, PEDF induced alkaline phosphatase (ALP) activity in MSCs at 14 days of incubation in maintenance medium; hMSCs incubated in osteogenic medium in presence of PEDF expressed 19% more ALP activity (35.655\u2009\u00b1\u20091.827 U\/mg protein, p\u2009=\u2009.041 than cells incubated in the same medium without PEDF supplementation (29.956\u2009\u00b1\u20092.100 U\/\u03bcg protein). hMSCs incubated in osteogenic medium in presence of PEDF deposited 50% more mineral (2.108\u2009\u00b1\u20090.306 OD\/ml per well per 1 \u00d7 104 cells per square centimeter, p\u2009=\u2009.017) than MSCs incubated in absence of the protein (1.398\u2009\u00b1\u20090.098 OD\/ml per well per 1 \u00d7 104 cells per square centimeter) as determined by Alizarin Red quantitation. Reduction in PEDF expression in MSCs by siRNA led to decreased ALP activity (33.552\u2009\u00b1\u20092.009 U\/ng protein of knockdown group vs. 39.269\u2009\u00b1\u20093.533 U\/ng protein of scrambled siRNA group, p\u2009=\u2009.039) and significant reduction in mineral deposition (0.654\u2009\u00b1\u20090.050 OD\/ml per well per 1 \u00d7 104 cells per square centimeter of knockdown group vs. 1.152\u2009\u00b1\u20090.132 OD\/ml per well per 1 \u00d7 104 cells per square centimeter of wild-type group, p\u2009=\u2009.010). Decreased ALP activity and mineral deposition were restored by supplementation with exogenous PEDF protein. PEDF activated ERK and AKT signaling pathways in MSCs to induce expression of osteoblastic-related genes. These data suggest that PEDF is involved in MSCs osteoblastic differentiation. Stem Cells \u00a02013;31:2714\u20132723<\/jats:p>","DOI":"10.1002\/stem.1505","type":"journal-article","created":{"date-parts":[[2013,8,13]],"date-time":"2013-08-13T11:23:52Z","timestamp":1376393032000},"page":"2714-2723","source":"Crossref","is-referenced-by-count":67,"title":["Pigment Epithelium-Derived Factor Enhances Differentiation and Mineral Deposition of Human Mesenchymal Stem Cells"],"prefix":"10.1093","volume":"31","author":[{"given":"Feng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation Division of Musculoskeletal Sciences Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation Division of Musculoskeletal Sciences Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Tombran-Tink","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Sciences Division of Musculoskeletal Sciences Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Niyibizi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation Division of Musculoskeletal Sciences Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA"},{"name":"Department of Biochemistry and Molecular Biology Division of Musculoskeletal Sciences Pennsylvania State University College of Medicine, Hershey, Pennsylvania, 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