Activation of PPARs Modulates Signalling Pathways and Expression of Regulatory Genes in Osteoclasts Derived from Human CD14+ Monocytes

Autor: Marlena C. Kruger, Magdalena Coetzee, Abe E. Kasonga
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Peroxisome Proliferator-Activated Receptors
Lipopolysaccharide Receptors
Osteoclasts
Peroxisome proliferator-activated receptor
Monocytes
PPAR agonist
lcsh:Chemistry
0302 clinical medicine
Receptor
lcsh:QH301-705.5
Cells
Cultured
Spectroscopy
chemistry.chemical_classification
biology
unsaturated fatty acid
RANKL signalling
General Medicine
Computer Science Applications
Cell biology
medicine.anatomical_structure
RANKL
030220 oncology & carcinogenesis
osteoclast
Fatty Acids
Unsaturated
lipids (amino acids
peptides
and proteins)
Signal Transduction
Adult
Macrophage colony-stimulating factor
musculoskeletal diseases
Peroxisome proliferator activated receptor
Adolescent
Article
Catalysis
Inorganic Chemistry
Young Adult
03 medical and health sciences
Osteoclast
medicine
Humans
Physical and Theoretical Chemistry
Molecular Biology
Unsaturated fatty acid
RANK Ligand
Organic Chemistry
osteoporosis
030104 developmental biology
Gene Expression Regulation
Nuclear receptor
chemistry
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Zdroj: International Journal of Molecular Sciences, Vol 20, Iss 7, p 1798 (2019)
International Journal of Molecular Sciences
Volume 20
Issue 7
ISSN: 1422-0067
Popis: Osteoclasts are the sole bone resorbing cell in the body and their over activity is key in the development of osteoporosis. Osteoclastogenesis is mediated by receptor activator of nuclear factor &kappa
B ligand (RANKL) signalling pathways. Unsaturated fatty acids (UFA) are known to inhibit osteoclastogenesis by targeting RANKL signalling. However, the mechanisms of action remain unclear. Peroxisome proliferator activated receptors (PPARs) are a family of nuclear receptors, with three known isoforms (PPAR-&alpha
PPAR-&beta
/&delta
and PPAR-&gamma
), that are known to bind UFAs and are expressed in osteoclasts. In this study, we aimed to determine how different families of UFAs activate PPARs and how PPAR activation influences osteoclast signalling. Human CD14+ monocytes were seeded into cluster plates with RANKL and macrophage colony stimulating factor (M-CSF) in the presence of PPAR agonists or different types of UFAs. All the PPAR agonists were shown to upregulate the activity of their respective receptors. Polyunsaturated fatty acids increased PPAR-&alpha
to a greater extent than monounsaturated fatty acids (MUFAs), which favoured PPAR-&beta
activation. All PPAR agonists inhibited osteoclastogenesis. The activation of RANKL signalling pathways and expression of key osteoclast genes were downregulated by PPAR agonists. This study reveals that PPAR activation can inhibit osteoclastogenesis through modulation of RANKL signalling.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje