| Theme |
Ectopic calcification on soft tissue: Vascular calcification and cardiac valvular calcification |
| Title |
Histochemical and ultrastructural evidences for vascular calcification -- Arterial calcification by defective FGF23/klotho signaling |
| Author |
Tomoka Hasegawa |
Developmental Biology of Hard Tissue, Graduate School of Dental Medicine and Faculty of Dental Medicine, Hokkaido University |
| Author |
Tomomaya Yamamoto |
Department of Dentistry, Japan Ground Self-Defense Force Camp Asaka |
| Author |
Hiromi Hongo |
Developmental Biology of Hard Tissue, Graduate School of Dental Medicine and Faculty of Dental Medicine, Hokkaido University |
| Author |
Yukina Miyamoto |
Developmental Biology of Hard Tissue, Graduate School of Dental Medicine and Faculty of Dental Medicine, Hokkaido University |
| Author |
Norio Amizuka |
Developmental Biology of Hard Tissue, Graduate School of Dental Medicine and Faculty of Dental Medicine, Hokkaido University |
| [ Summary ] |
FGF23 secreted by osteocytes circulates to the proximal renal tubules and binds the FGFR1c/klotho receptor complex to regulate the serum concentration of inorganic phosphate (Pi). Therefore, the defective FGF23/klotho axis in kl/kl mice results in hypercalcemia and hyperphosphatemia, often exhibiting Möncheberg's vascular calcification in the aorta. The assumed mechanism of vascular calcification shown in kl/kl mice is that, in a defective circumstance of FGF23/klotho axis, vascular smooth muscle cells undergo a phenotypic differentiation into osteoblasts enough to induce matrix vesicle-mediated biological calcification. Under transmission electron microscopic observation, there were many matrix vesicle-like structures underneath osteoblasts, but unlike normal bone calcification, these matrix vesicle-like structures were often associated with extracellular fibrils of elastic laminar, rather than typeⅠ collagen fibrils. When kl/kl mice were given a low phosphate diet, vascular calcification was markedly-inhibited. However, kl/kl mice fed with a low phosphate diet showed not only the reduced level of serum Pi, but also the recovered gene expression of α klotho, both of which mechanisms may be involved in inhibited calcification of kl/kl aorta. |