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Activation of PPARs Modulates Signalling Pathways and Expression of Regulatory Genes in Osteoclasts Derived from Human CD14+ Monocytes.
Kasonga, Abe; Kruger, Marlena C; Coetzee, Magdalena.
Afiliação
  • Kasonga A; Department of Physiology, University of Pretoria, Pretoria 0001, South Africa. abe.kasonga@up.ac.za.
  • Kruger MC; School of Health Sciences, College of Health, Massey University, Palmerston North 4442, New Zealand. m.c.kruger@massey.ac.nz.
  • Coetzee M; Institute for Food, Nutrition and Well-being, University of Pretoria, Pretoria 0001, South Africa. m.c.kruger@massey.ac.nz.
Int J Mol Sci ; 20(7)2019 Apr 11.
Article em En | MEDLINE | ID: mdl-30979019
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 κB 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-α, PPAR-ß/δ and PPAR-γ), 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-α to a greater extent than monounsaturated fatty acids (MUFAs), which favoured PPAR-ß/δ 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoclastos / Monócitos / Transdução de Sinais / Receptores de Lipopolissacarídeos / Receptores Ativados por Proliferador de Peroxissomo / Ácidos Graxos Insaturados Limite: Adolescent / Adult / Humans / Male Idioma: En Revista: Int J Mol Sci Ano de publicação: 2019 Tipo de documento: Article País de afiliação: África do Sul

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoclastos / Monócitos / Transdução de Sinais / Receptores de Lipopolissacarídeos / Receptores Ativados por Proliferador de Peroxissomo / Ácidos Graxos Insaturados Limite: Adolescent / Adult / Humans / Male Idioma: En Revista: Int J Mol Sci Ano de publicação: 2019 Tipo de documento: Article País de afiliação: África do Sul