Article
Active vitamin D hormone inhibits anti-osteogenic effects of TNF-alpha on human osteoblasts
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Authors
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Peter Oelzner
- Universitätsklinikum Jena, Klinik für Innere Medizin III, Abteilung Rheumatologie/Osteologie, Jena
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Sybille Franke
- Universitätsklinikum Jena, Klinik für Innere Medizin III, Abteilung Rheumatologie/Osteologie, Jena
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Ivonne Löffler
- Universitätsklinikum Jena, Klinik für Innere Medizin III, Jena
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Gunther Hofmann
- Universitätsklinikum Jena, Klinik für Unfall-, Hand- und Wiederherstellungschirurgie, Jena
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Gunter Wolf
- Universitätsklinikum Jena, Klinik für Innere Medizin III, Jena
| Published: | February 5, 2019 |
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Outline
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Background: Suppression of osteoblast (OB) differentiation and function by proinflammatory cytokines such as tumour necrosis factor alpha (TNFα) is an important mechanism of inflammation associated bone loss. Vitamin D deficiency is frequently observed in chronic inflammatory diseases. In rheumatoid arthritis as well as in ankylosing spondylitis a highly significant decrease of serum levels of the active vitamin D hormone 1.25-dihydroxyvitamin D3 (1.25D3) with increasing disease activity has been proven. Because 1.25D3 has osteoanabolic effects on mature OB, the question arises if 1.25D3 is able to antagonize TNFα-induced functional alterations in OB.
Methods: Human OB were isolated and cultured from bone tissue of 10 patients with knee osteoarthritis and joint replacement. Cells from passages 3–7 were treated for 48 hours with fetal calf serum (control), 1.25D3 (500 pmol/l) and TNFα in two different concentrations (1 ng/ml and 10 ng/ml) and with a combination of 1.25D3 and TNFα. mRNA and protein expression of bone alkaline phosphatase (bALP), collagen type 1 (Col1) and osteocalcin (OC) as well as of 1-alpha-hydroxylase in OB were investigated by quantitative real-time PCR and Western Blot-analysis, respectively.
Results: In comparison to control OB mRNA expression (p<0.001) and protein expression (p</=0.01) of AP, Col1 and OC were stimulated by 1.25D3 and suppressed by both TNFα concentrations. Combination of 1,25D3 with TNFα inhibited completely the suppressive effect of TNFα on mRNA and protein expression of the three osteoblastic markers. Both 1.25D3 and TNFα as well as the combination of 1.25D3 and TNFα resulted in an increase in mRNA and protein expression of 1-α-hydroxylase (p<0,01).
Conclusion: Active vitamin D hormone antagonizes suppressive effects of TNFα on selective OB functions in vitro. Because 25-hydroxyvitamin D3 is metabolized into 1.25D3 in OB and this metabolisation is regularly substrate dependent, vitamin D deficiency in chronic inflammation with increased TNFα production may result in a particularly unfavourable effect on bone formation. Induction of 1-α-hydroxylase by TNFα in OB is different from TNFα effects on other cells and may reflect a mechanism to limit TNFα effects on human OB.
