Hypoxia and vitamin D differently contribute to leptin and dickkopf-related protein 2 production in human osteoarthritic subchondral bone osteoblasts

Bone remodelling and increased subchondral densification are important in osteoarthritis (OA). Modifications of bone vascularisation parameters, which lead to ischemic episodes associated with hypoxic conditions, have been suspected in OA. Among several factors potentially involved, leptin and dickk...

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Published in:Arthritis research & therapy 2014-10, Vol.16 (5), p.459-459, Article 459
Main Authors: Bouvard, Béatrice, Abed, Elie, Yéléhé-Okouma, Mélissa, Bianchi, Arnaud, Mainard, Didier, Netter, Patrick, Jouzeau, Jean-Yves, Lajeunesse, Daniel, Reboul, Pascal
Format: Article
Language:English
Subjects:
Aged
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - metabolism
Biochemistry
Biochemistry, Molecular Biology
Bone and Bones - pathology
Cell Hypoxia
Cells, Cultured
Enzyme-linked immunosorbent assay
Female
Gene Expression - genetics
Genes
Human health and pathology
Humans
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Immunoblotting
Intercellular Signaling Peptides and Proteins - genetics
Intercellular Signaling Peptides and Proteins - metabolism
Leptin - genetics
Leptin - metabolism
Life Sciences
Male
Middle Aged
Mitogens
Molecular biology
Osteoarthritis - pathology
Osteoblasts - drug effects
Osteoblasts - metabolism
Osteocalcin - genetics
Osteocalcin - metabolism
p38 Mitogen-Activated Protein Kinases - metabolism
Phosphatidylinositol 3-Kinases - metabolism
Protein kinases
Reverse Transcriptase Polymerase Chain Reaction
RNA Interference
Signal Transduction - drug effects
Signal Transduction - genetics
Vitamin D - pharmacology
Vitamins - pharmacology
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Summary:Bone remodelling and increased subchondral densification are important in osteoarthritis (OA). Modifications of bone vascularisation parameters, which lead to ischemic episodes associated with hypoxic conditions, have been suspected in OA. Among several factors potentially involved, leptin and dickkopf-related protein 2 (DKK2) are good candidates since they are up-regulated in OA osteoblasts (Obs). Therefore, in the present study, we investigated the hypothesis that hypoxia may drive the expression of leptin and DKK2 in OA Obs. Obs from the sclerotic portion of OA tibial plateaus were cultured either under 20% or 2% oxygen tension in the presence or not of 50 nM of 1,25-dihydroxyvitamin D3 (VitD3). The expression of leptin, osteocalcin, DKK2, hypoxia-inducible factors (Hif)-1α and -2α was measured by real-time polymerase chain reaction and leptin production by enzyme-linked immunosorbent assay (ELISA). The expression of Hif-1α, Hif-2α, leptin and DKK2 was reduced using silencing (si) RNA technique. Signalling pathway of hypoxia-induced leptin was investigated by western blotting and mitogen-activated protein kinase (MAPK) inhibitors. As expected, hypoxia stimulated the expression of Hif-1 and Hif-2. The expression of leptin and DKK2 in Obs was also stimulated 7-fold and 1.8-fold respectively (p
ISSN:1478-6354
1478-6362
1478-6354
DOI:10.1186/s13075-014-0459-3