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Cartilage. 2012 Jan;3(1):100-3. doi: 10.1177/1947603511405837.

Influence of Tumor Necrosis Factor α, Parathyroid Hormone, and Vitamin D3 on Modulation of the RANKL2 Isoform: A Pilot Study.

Cartilage

Steeve Kwan Tat, Jean-Pierre Pelletier, Carmen Ruiz-Velasco, Marc Padrines, Yannick Fortun, François Mineau, Johanne Martel-Pelletier

Affiliations

  1. Osteoarthritis Research Unit, Notre-Dame Hospital, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada.
  2. Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, INSERM ER17, Faculté de Médecine, Université de Nantes, Nantes, France.

PMID: 26069623 PMCID: PMC4297191 DOI: 10.1177/1947603511405837

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.

Keywords: PTH; RANKL2 isoform; TNF-α; bone; cytokines and growth factors; osteoarthritis disease modification; preclinical research; vitamin D3

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