LPA induces osteoblast differentiation through interplay of two receptors: LPA1 and LPA4
| Autor: | Paul J. Yaworsky, Yogendra Kharode, Yao-Bin Liu, Julia Billiard, Peter V.N. Bodine, John A. Robinson |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Biology Biochemistry Bone and Bones Small hairpin RNA Mice chemistry.chemical_compound Osteogenesis Internal medicine Lysophosphatidic acid Cyclic AMP medicine Animals Humans Receptors Lysophosphatidic Acid Receptor Molecular Biology Cells Cultured Mice Knockout Osteoblasts Receptors Purinergic P2 Mesenchymal stem cell Receptors Purinergic Cell Differentiation Mesenchymal Stem Cells Osteoblast Cell Biology In vitro Cell biology medicine.anatomical_structure Endocrinology chemistry Calcium lipids (amino acids peptides and proteins) Lysophospholipids Signal transduction Stem cell |
| Zdroj: | Journal of Cellular Biochemistry. |
| ISSN: | 1097-4644 0730-2312 |
| Popis: | The bioactive phospholipid, lysophosphatidic acid (LPA), acting through at least five distinct receptors LPA1-LPAS, plays important roles in numerous biological processes. Here we report that LPA induces osteoblastic differentiation of human mesenchymal stem cells hMSC-TERT. We find that hMSC-TERT mostly express two LPA receptors, LPA1 and LPA4, and undergo osteoblastic differentiation in serum-containing medium. Inhibition of LPA1 with Ki16425 completely abrogates osteogenesis, indicating that this process is mediated by LPA in the serum through activation of LPA1. In contrast to LPA1, down-regulation of LPA4 expression with shRNA significantly increases osteogenesis, suggesting that this receptor normally exerts negative effects on differentiation. Mechanistically, we find that in hMSC-TERT, LPA induces a rise in both cAMP and Ca 2+ . The rise in Ca 2+ is completely abolished by Ki16425, whereas LPA-mediated cAMP increase is not sensitive to Ki 16425. To test if LPA signaling pathways controlling osteogenesis in vitro translate into animal physiology, we evaluated the bones of LPA4-deficient mice. Consistent with the ability of LPA4 to inhibit osteoblastic differentiation of stem cells, LPA4-deficient mice have increased trabecular bone volume, number, and thickness. |
| Databáze: | OpenAIRE |
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