Oleoyl serine, an endogenous N-acyl amide, modulates bone remodeling and mass
| Autor: | Bo Tan, David K. O’Dell, Malka Attar-Namdar, Arik Bar, Alon Bajayo, Michael Walker, Jordyn Stuart, Garry Milman, Joseph Tam, Raphael Mechoulam, Heather B. Bradshaw, Reem Smoum, Orr Ofek, Vardit Kram, Itai Bab |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Materials science Bone density Blotting Western Oleic Acids Bone tissue Bone resorption Mass Spectrometry Bone remodeling Cell Line Receptors G-Protein-Coupled Mice Osteoclast Bone Density Internal medicine medicine Serine Animals Chromatography High Pressure Liquid Analysis of Variance Multidisciplinary Mitogen-Activated Protein Kinase 3 Osteoblasts biology Osteoblast Biological Sciences Amides Mice Inbred C57BL medicine.anatomical_structure Endocrinology RANKL biology.protein Osteoporosis Bone marrow Bone Remodeling |
| Popis: | Bone mass is determined by a continuous remodeling process, whereby the mineralized matrix is being removed by osteoclasts and subsequently replaced with newly formed bone tissue produced by osteoblasts. Here we report the presence of endogenous amides of long-chain fatty acids with amino acids or with ethanolamine ( N -acyl amides) in mouse bone. Of these compounds, N -oleoyl- l -serine (OS) had the highest activity in an osteoblast proliferation assay. In these cells, OS triggers a Gi-protein-coupled receptor and Erk1/2. It also mitigates osteoclast number by promoting osteoclast apoptosis through the inhibition of Erk1/2 phosphorylation and receptor activator of nuclear-κB ligand (RANKL) expression in bone marrow stromal cells and osteoblasts. In intact mice, OS moderately increases bone volume density mainly by inhibiting bone resorption. However, in a mouse ovariectomy (OVX) model for osteoporosis, OS effectively rescues bone loss by increasing bone formation and markedly restraining bone resorption. The differential effect of exogenous OS in the OVX vs. intact animals is apparently a result of an OVX-induced decrease in skeletal OS levels. These data show that OS is a previously unexplored lipid regulator of bone remodeling. It represents a lead to antiosteoporotic drug discovery, advantageous to currently available therapies, which are essentially either proformative or antiresorptive. |
| Databáze: | OpenAIRE |
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