Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Histochemical examination on calcification in bone and arteries in kl/kl mice and aklotho-/- mice fed with phosphate-insufficient diet (#271)

Tomoka Hasegawa 1 , Kumiko Hayashibara 1 , Tomomaya yamamoto 1 , Hiromi Hongo 1 , Kanako Tsuboi 1 , Norio Amizuka 1
  1. Dept. of Develop. Biol. Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, HOKKAIDO, Japan

FGF23/klotho plays a pivotal role in regulating serum concentration of phosphate by cooperating with kidney, and the disturbed signaling of FGF23/klotho results in elevated concentration of serum calcium and phosphate, inducing osteomalacia-like phenotype and vascular calcification. It seems of importance to clarify which of elevated concentration of serum phosphate or the disturbed autocrine/paracrine manner of FGF23/klotho axis would predominantly give rise to abnormal calcification in bone and arteries.  In this study, we have histochemically examined calcification in bone and arteries of wild-type mice, kl/kl mice and aklotho-/- mice fed with phosphate-insufficient diet.

Kl/kl mice and aklotho-/- mice fed with normal diet showed broad uncalcified area of epiphyseal bone matrix, and there were many calcified osteocytic lacunae in the uncalcified bone.  The calcified osteocytic lacunae revealed an intense immunoreactivity of DMP-1, which has been reported to have an affinity to crystalline calcium. In contrast, when fed with phosphate insufficient diet, kl/kl mice demonstrated elevated expression of klotho in kidney, while aklotho-/- mice did not show klotho gene.  As a consequence, kl/kl mice fed with phosphate insufficient diet recovered from abnormal bone matrix to some extent, e.g., showing well-calcified bone matrix with intact osteocytic lacunae. Unlikely, aklotho-/- mice fed with insufficient phosphate-diet still showed the abovementioned abnormal bone. Arteries of kl/kl mice fed with insufficient phosphate diet did not show broad vascular calcification, but instead, there seemed cartilage-like tissue including chondrocytes embedded in type II collagen-positive matrix. Unlike kl/kl mice, however, aklotho-/- mice fed with insufficient phosphate diet still demonstrated calcification in the arteries.

Thus, aklotho-/- mice did not recover from histopathological abnormalities in bone and arteries by means of insufficient phosphate diet.  There seems a possibility that FGF23/klotho axis may influence bone and arteries by mediating an autocrine/paracrine pathway, rather than by regulating serum phosphate.