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Aktuelle Rheumatologie 2014; 39(06): 384-392
DOI: 10.1055/s-0034-1384553
Übersichtsarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Advanced glycation endproducts (AGEs) und Vitamin D – antagonistische Prinzipien im Knochenstoffwechsel?

Advanced Glycation Endproducts (AGEs) and Vitamin D – Antagonistic Principles in Bone Metabolism?
P. Oelzner
1   Klinik für Innere Medizin III, Universitätsklinikum Jena, Jena
,
S. Franke
1   Klinik für Innere Medizin III, Universitätsklinikum Jena, Jena
,
G. Wolf
1   Klinik für Innere Medizin III, Universitätsklinikum Jena, Jena
› Author Affiliations
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Publication History

Publication Date:
17 December 2014 (online)

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Zusammenfassung

Der physiologische Knochenumbau dient der Anpassung des Knochens an mechanische Belastung und gewährleistet die Stabilität des Skeletts. Differenzierung und Funktion der am Knochenumbau beteiligten Zellen werden durch eine Vielzahl von Hormonen, Zytokinen und anderen Faktoren reguliert. Zu diesen Substanzen zählen u. a. advanced glycation endproducts (AGEs) und Vitamin D. Verschiedene Befunde weisen auf antagonistische Funktionen von AGEs und Vitamin D im Knochenstoffwechsel hin. Die Differenzierung von Osteoblasten sowie die Expression osteogener Marker werden durch AGEs gehemmt und durch Vitamin D stimuliert. In diesem Zusammenhang sind inhibitorische Effekte von AGEs auf die für die Osteoblasten-Differenzierung bedeutsamen Transkriptionsfaktoren Runx2 und Osterix sowie auf den Wnt-Signalweg von Bedeutung. Vitamin D hat dagegen einen stimulierenden Einfluss auf die Expression der genannten Transkriptionsfaktoren sowie das Wnt-Signaling. AGEs hemmen die Knochenmineralisation, während Vitamin D insbesondere vor dem Hintergrund einer chronischen Inflammation die Mineralisation fördert. Die Effekte von AGEs und Vitamin D auf die Knochenresorption sind komplex. Die Induktion von RANKL in Osteoblasten durch AGEs, eine reduzierte Knochenresorption in AGE-defizienten Mäusen und die Abnahme der RANKL/OPG-Ratio im Rahmen der Vitamin D-stimulierten Osteoblasten-Differenzierung als auch komplexe Effekte von Vitamin D auf Osteoklasten-Differenzierung und das RANK-Signaling sprechen für eine Steigerung der Knochenresorption durch AGEs und eine Hemmung derselben durch Vitamin D. Antagonistische Wirkungen von AGEs und Vitamin D gewinnen auch durch die Koinzidenz von AGE-Akkumulation und Vitamin D-Mangel im höheren Lebensalter sowie bei verschiedenen Erkrankungen wie Osteoporose, Rheumatoider Arthritis, Diabetes mellitus und chronischer Niereninsuffizienz klinische Bedeutung. Ferner gibt es Hinweise für direkte Interaktionen der AGE- und Vitamin D-assoziierten Signalwege. Wir konnten in Untersuchungen an humanen Osteoblasten nachweisen, dass antiosteogene Effekte von AGEs durch Vitamin D-Hormon komplett antagonisiert werden. Dabei sind wahrscheinlich komplexe Effekte von Vita­min D-Hormon auf das RAGE-NFκB-vermittelte Signaling von Bedeutung. In der folgenden Übersicht soll auf die potentiell antagonistischen Effekte von AGEs und Vitamin D im Knochenstoffwechsel eingegangen und die klinische Bedeutung dieser Interaktionen herausgearbeitet werden.

Abstract

Physiological bone remodelling is of critical importance for adaptation of bone to mechanical load and ensures the stability of the skeleton. Differentiation and function of cells involved in bone remodelling are regulated by a variety of hormones, cytokines and other factors. Both advanced glycation endproducts (AGEs) and vitamin D belong to these substances. Various data indicate an antagonistic function of AGEs and vitamin D in bone remodelling. The differentiation of osteoblasts and the expression of osteogenic markers is inhibited by AGEs and stimulated by vitamin D. In this context, inhibitory effects of AGEs on transcription factors important for differentiation of osteoblasts such as Runx2 and Osterix as well as on wnt-signalling are of significance, whereas vitamin D promotes the expression of these transcription factors and the wnt-signalling. The mineralisation process of the bone is inhibited by AGEs but augmented by vitamin D, especially against the backdrop of chronic inflammation. The effects of AGEs and vitamin D on bone resorption are complex. The induction of RANKL in osteoblasts by AGEs, a reduced bone resorption in AGE-deficient mice and the decrease of the RANKL/OPG-ratio due to vitamin D driven differentiation of osteoblasts as well as complex effects of vitamin D on differentiation of osteoclasts and on RANK-signalling are in accordance with a stimulation of bone resorption by AGEs and with an antiresorptive effect of vitamin D. Antagonistic effects of AGEs and vitamin D gain clinical significance by the coincidence of AGE accumulation and vitamin D deficiency in older age and in various diseases such as osteoporosis, rheumatoid arthritis, diabetes and chronic renal failure. Furthermore, some findings indicate direct interactions between AGE- and vitamin D-associated signalling. We were able to demonstrate that anti-osteogenic effects of AGEs on human osteoblasts are completely prevented by vitamin D hormone. Complex effects of vitamin D hormone on RAGE-NFκB-signalling are probably of critical significance in this process. The following overview is focused on potential antagonistic effects of AGEs and vitamin D in bone metabolism including the clinical significance of these interactions.

Schlüsselwörter

Advanced glycation end products - Vitamin D - Knochenstoffwechsel

Key words

advanced glycation end products - vitamin D - bone metabolism
 

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