title: Effect of retinoic acid and vitamin D3 on osteoblast differentiation and activity in aging.
abstract: Several studies have evidenced that in aging, osteoblast functional activity is impaired: osteoblast proliferation is slower and matrix deposition is less efficient. Because peroxisome-proliferator-activated receptor γ2 (PPARγ2) and fatty acids are important inhibitory signals in osteoblast development, we have investigated in human primary osteoblasts obtained from patients of different ages, the influence of retinoic acid and calcitriol on enzymes involved in differentiative (PPARγ2, β-catenin, and insulin-like growth factor 1) and metabolic (carnitine palmitoyltransferase 1) intracellular pathways, and on transglutaminase 2, as enzyme fundamental for stabilizing the newly deposited extracellular matrix in bone. Retinoic acid and calcitriol influenced, respectively, proliferation and differentiation of osteoblasts, and an increase in PPARγ2 expression was observed following retinoic acid administration, whereas a decrease was observed following calcitriol administration. Aging widely influenced all parameters analyzed (the proliferation, differentiation, and new matrix deposition are significantly reduced in aged osteoblasts), with the exception of PPARγ2, which we found to be constitutively overexpressed and not modulated by retinoic acid or calcitriol administration. Our findings show the impaired ability of aged osteoblasts to perform adequate functional response and draw attention to the therapeutic approaches for bone healing in elderly patients.
authors.affiliation: Pharmacy Science Department, University of Eastern Piedmont, Alessandria, Novara, Vercelli, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Bosetti
authors.affiliation: Department of Health Sciences, University of Eastern Piedmont, Alessandria, Novara, Vercelli, Italy. maurizio.sabbatini@med.unipmn.it.|Dipartmento Scienze della Salute, Università del Piemonte Orientale "Amedeo Avogadro", via Solaroli 17, 28100, Novara, Italy. maurizio.sabbatini@med.unipmn.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sabbatini
authors.affiliation: Institute of Protein Biochemistry, CNR, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Calarco
authors.affiliation: Department of Health Sciences, University of Eastern Piedmont, Alessandria, Novara, Vercelli, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Borrone
authors.affiliation: Institute of Protein Biochemistry, CNR, Naples, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Peluso
authors.affiliation: Department of Health Sciences, University of Eastern Piedmont, Alessandria, Novara, Vercelli, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cannas
mesh_terms: D000375:Aging / Q000502:physiology*; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects*; D047495:PPAR gamma / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D047495:PPAR gamma; D051176:beta Catenin; D002762:Cholecalciferol; D014212:Tretinoin; D007334:Insulin-Like Growth Factor I; D002334:Carnitine O-Palmitoyltransferase
keywords: Calcitriol; Carnitine palmitoyltransferase 1; Human primary osteoblasts; Peroxisome-proliferator-activated receptor gamma; Transglutaminase