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Free fatty acid receptor 4-β-arrestin 2 pathway mediates the effects of different classes of unsaturated fatty acids in osteoclasts and osteoblasts
- Source :
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1864:281-289
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Bone is a dynamic tissue that is constantly remodelled by bone resorbing osteoclasts and bone forming osteoblasts, respectively. A breakdown in the remodelling process underlies several bone diseases such as osteoporosis. Unsaturated fatty acids (UFAs) have been shown to have beneficial effects on bone health. However, the mechanism of action of UFAs in bone remains unclear. Free fatty acid receptor 4 (FFAR4) is expressed in bone cells and preferentially binds ω-3 and ω-7 UFAs. Therefore, we sought to determine if FFAR4 influenced the action of different classes of UFAs in bone cells. FFAR4 and potential signalling pathways, β-arrestin 2 (βarr2) and Gαq, were silenced in RAW264.7 murine macrophages (pre-osteoclasts) and MC3T3-E1 murine pre-osteoblasts. Cell differentiation, activation of signalling pathways and expression of regulatory genes were evaluated. The ω-3 UFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and the ω-7 UFA, palmitoleic acid (PLA), were shown to require the FFAR4/βarr2 signalling pathway to inhibit osteoclast differentiation in RAW264.7 murine macrophages. The ω-6 UFA, arachidonic acid, and the ω-9 UFA, oleic acid (OA), were shown to inhibit osteoclast formation but did not use FFAR4. DHA, EPA, PLA and OA enhanced osteoblast signalling through the FFAR4/βarr2 signalling axis. This study reveals that FFAR4/βarr2 signalling may mediate the bone protective effects of different classes of UFAs in osteoclasts and osteoblasts.
- Subjects :
- 0301 basic medicine
Docosahexaenoic Acids
Arrestins
Cellular differentiation
Osteoclasts
Fatty Acids, Nonesterified
Receptors, G-Protein-Coupled
Fatty Acids, Monounsaturated
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Osteogenesis
Osteoclast
Fatty Acids, Omega-3
Bone cell
medicine
Animals
Palmitoleic acid
Molecular Biology
Arachidonic Acid
Osteoblasts
RANK Ligand
Cell Differentiation
Osteoblast
Cell Biology
beta-Arrestin 2
Eicosapentaenoic acid
Cell biology
RAW 264.7 Cells
030104 developmental biology
medicine.anatomical_structure
Eicosapentaenoic Acid
chemistry
Docosahexaenoic acid
030220 oncology & carcinogenesis
Fatty Acids, Unsaturated
Arachidonic acid
Oleic Acid
Signal Transduction
Subjects
Details
- ISSN :
- 13881981
- Volume :
- 1864
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
- Accession number :
- edsair.doi.dedup.....0c56eef684a9dced245d41828abf69d9