Histochemical Examination on Periodontal Tissues of Klotho-Deficient Mice Fed With Phosphate-Insufficient Diet

Abstract

To elucidate which of elevated serum concentration of inorganic phosphate (Pi) or disrupted signaling linked to αklotho/fibroblast growth factor 23 (FGF23) is a predominant regulator for senescence-related degeneration seen in αKlotho-deficient mice, we have examined histological alteration of the periodontal tissues in the mandibular interalveolar septum of αKlotho-deficient mice fed with Pi-insufficient diet. We prepared six groups of mice: wild-type, kl/kl, and αKlotho mice with normal diet or low-Pi diet. As a consequence, kl/kl and αKlotho mice showed the same abnormalities in periodontal tissues: intensely stained areas with hematoxylin in the interalveolar septum, dispersed localization of alkaline phosphatase-positive osteoblasts and tartrate-resistant acid phosphatase-reactive osteoclasts, and accumulation of dentin matrix protein 1 in the osteocytic lacunae. Although kl/kl mice improved these histological abnormalities, αKlotho mice failed to normalize those. Gene expression of αKlotho was shown to be increased in kl/kl specimens. It seems likely that histological abnormalities of kl/kl mice have been improved by the rescued expression of αKlotho, rather than low concentration of serum Pi. Thus, the histological malformation in periodontal tissues in αKlotho-deficient mice appears to be due to not only increased concentration of Pi but also disrupted αklotho/FGF23 signaling.

Klotho inhibits H2O2‐induced oxidative stress and apoptosis in periodontal ligament stem cells by regulating UCP2 expression

“…Soluble klotho has been reported to attenuate myocardial hypertrophy induced by FGF23 in mice 16 . Additionally, the klotho/FGF23 signalling pathway is expressed abnormally in the klotho‐deficient mice with periodontitis 17 . Recently, the role of klotho in periodontitis is attracting ever‐increasing attention.…”

“…Uncoupling protein 2 (UCP2), a member of the mitochondrial transporters family, has been reported to be involved in metabolic reprogramming 15,16 . The ability of UCP2 to regulate glucose is strongly associated with cellular proliferation and apoptosis 17 . Additionally, the UCP2 upregulation might significantly suppress the proliferation and migration of vascular smooth muscle cells by inhibiting oxidative stress 18,19 .…”

Role of sodium‐dependent Pi transporter/Npt2c on Pi homeostasis in klotho knockout mice different properties between juvenile and adult stages

“…Deletion of Npt2c in KLKO mice did not have a clear recovery effect on bone phenotype. In addition, bone abnormalities in KLKO mice may have been caused by factors such as increased FGF23 due to klotho deficiency rather than suppression of plasma Pi levels, as described previously (Hikone et al, 2017).…”

Phylogenetic analysis and expression profiling of the Klotho gene family in the short-lived African killifish Nothobranchius furzeri

“…This expression site may be linked to mineralization of hard tissue considering the importance of α Klotho in electrolyte homeostasis. Indeed, mice lacking functional Klotho gene display tooth malformations (Hikone et al 2017 ).

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