Determination of mesenchymal stem cell fate by pigment epithelium‐derived factor (PEDF) results in increased adiposity and reduced bone mineral content
| Autor: | Arijeet K. Gattu, Thomas O. Carpenter, Matthew S. Rodeheffer, Ryan Berry, E. Scott Swenson, Yasuko Iwakiri, Varman T. Samuel, Chuhan Chung, Nancy Troiano, Christopher D. Church |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Peroxisome proliferator-activated receptor Adipose tissue Biology Biochemistry Research Communications Cell Line Mice chemistry.chemical_compound PEDF Bone Density Adipocyte Internal medicine Adipocytes Genetics medicine Animals Humans Nerve Growth Factors Eye Proteins Wnt Signaling Pathway Molecular Biology Cells Cultured Serpins Adiposity Mice Knockout chemistry.chemical_classification Adipogenesis Osteoblasts Mesenchymal stem cell Wnt signaling pathway Mesenchymal Stem Cells Osteoblast PPAR gamma Wnt Proteins Endocrinology medicine.anatomical_structure chemistry Adiponectin Biotechnology |
| Zdroj: | The FASEB Journal. 27:4384-4394 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.13-232900 |
| Popis: | Pigment epithelium-derived factor (PEDF), the protein product of the SERPINF1 gene, has been linked to distinct diseases involving adipose or bone tissue, the metabolic syndrome, and osteogenesis imperfecta (OI) type VI. Since mesenchymal stem cell (MSC) differentiation into adipocytes vs. osteoblasts can be regulated by specific factors, PEDF-directed dependency of murine and human MSCs was assessed. PEDF inhibited adipogenesis and promoted osteoblast differentiation of murine MSCs, osteoblast precursors, and human MSCs. Blockade of adipogenesis by PEDF suppressed peroxisome proliferator-activated receptor-γ (PPARγ), adiponectin, and other adipocyte markers by nearly 90% compared with control-treated cells (P50% compared with controls, illustrating its systemic role as a negative regulator of adipogenesis. Bones from KO mice demonstrated a reduction in mineral content recapitulating the OI type VI phenotype. These results demonstrate that the human diseases associated with PEDF reflect its ability to modulate MSC differentiation.—Gattu, A. K., Swenson, E. S., Iwakiri, Y., Samuel, V. T., Troiano, N., Berry, R., Church, C. D., Rodeheffer, M. S., Carpenter, T. O., Chung, C. Determination of mesenchymal stem cell fate by pigment epithelium-derived factor (PEDF) results in increased adiposity and reduced bone mineral content. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text