科研之友
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摘要
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-NF kappa B-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.
- 出版日期2014-12
