title: Influence of Tumor Necrosis Factor α, Parathyroid Hormone, and Vitamin D3 on Modulation of the RANKL2 Isoform: A Pilot Study.
abstract: RANKL exists as three isoforms: RANKL1, 2, and 3. RANKL1 and 3 were reported to be differently expressed upon treatment with some osteotropic factors, but RANKL2 expression could not be reliably determined. Here, we investigated through a mechanistic model, human 293 cells stably transfected with the RANKL2cDNA, the production and modulation of RANKL2 protein stability upon treatment with TNF-α, vitamin D3, and PTH. Data showed that TNF-a significantly increased (p<0.03) RANKL2 production and its half-life/stability (p<0.005). Vitamin D3 and PTH had no effect. This information will help to better define and differentiate the pathological mechanisms operating during osteolytic diseases.
authors.affiliation: Osteoarthritis Research Unit, Notre-Dame Hospital, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada.
authors.forename: Steeve Kwan
authors.initials: SK
authors.lastname: Tat
authors.affiliation: Osteoarthritis Research Unit, Notre-Dame Hospital, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pelletier
authors.affiliation: Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, INSERM ER17, Faculté de Médecine, Université de Nantes, Nantes, France.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ruiz-Velasco
authors.affiliation: Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, INSERM ER17, Faculté de Médecine, Université de Nantes, Nantes, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Padrines
authors.affiliation: Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, INSERM ER17, Faculté de Médecine, Université de Nantes, Nantes, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Fortun
authors.affiliation: Osteoarthritis Research Unit, Notre-Dame Hospital, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Mineau
authors.affiliation: Osteoarthritis Research Unit, Notre-Dame Hospital, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada.
authors.forename: Johanne
authors.initials: J
authors.lastname: Martel-Pelletier
keywords: PTH; RANKL2 isoform; TNF-α; bone; cytokines and growth factors; osteoarthritis disease modification; preclinical research; vitamin D3