Role of Membrane-Bound Phosphatase in the Balance Between Osteoclastogenesis and Adipogenesis Under Local Phosphorus Environment — ASN Events
  1. Schedule
  2. Poster Session 2
  3. Role of Membrane-Bound Phosphatase in the Balance Between Osteoclastogenesis and Adipogenesis Under Local Phosphorus Environment

Role of Membrane-Bound Phosphatase in the Balance Between Osteoclastogenesis and Adipogenesis Under Local Phosphorus Environment (#227)

Keito Matsubayashi 1 , Reiri Hikihara 1 , Hitoki Yamanaka 2 , Ritsuko Masuyama 1
  1. Graduate School of Gastronomy Management, Ritsumeikan University, Kusatsu, Shiga, Japan
  2. Shinshu University, Matsumoto, Nagano, Japan

Background/aim

Ectoenzyme nucleotide pyrophosphatase/phosphodiesterase1(ENPP1) produces pyrophosphate by ATP degradation. Deficiency of ENPP1 activity reduced both serum phosphate and bone mass in mice, increased serum FGF23, and accelerated ectopic calcification in soft tissue. These characteristics suggest that the action of FGF23 is a major regulator of phosphate homeostasis by phosphate excretion. Furthermore, since the enzymatic activity of ENPP1 contributes to the supply of inorganic phosphate in the extracellular matrix niche, systemic phosphate homeostasis may be influenced by local phosphate metabolism mediated by ENPP1. To determine whether this local phosphate metabolism contributes to systemic phosphate homeostasis, we investigated the dynamic regulation of phosphate metabolism in mice lacking ENPP1 activity.

Methods

Dynamic phosphate metabolism and bone homeostasis were assessed in mice with ENPP1 deficiency (ENPP1asj). Furthermore, ENPP1asj mice were crossed to vitamin D receptor knockout mice (VDRKO) to generate double knockout mice (DKO) which impaired FGF23 production and verified FGF23 involvement in local phosphate metabolism.

Results

Compared to wild type (WT), ENPP1asj displayed hypophosphatemia accompanying increased FGF23 in 8-week-old. Apparent phosphate absorption was not changed by ENPP1 activity. In contrast, these values were decline in VDRKO. Remarkably, apparent phosphate absorption was improved in DKO although VDR activity lacked, and serum phosphate remained low. We therefore hypothesized that phosphate homeostasis was affected by other factors except for excretion and intestinal absorption. Next, to investigate phosphate source, bone resorption was assessed. Osteoclast number/surface was increased in ENPP1asj. As previously reported, osteoclast number/surface was significantly decreased in VDRKO, but improved in DKO to the level of WT, suggesting ENPP1 activity directly influence on osteoclast development. Osteoclast differentiation from bone marrow macrophage was upregulated by ENPP1 blockade or reduction of phosphate concentration in culture medium.

Conclusion

The activity of ENPP1 directly supports osteoclast development and alters local phosphate homeostasis and this pathway involved in systemic phosphate homeostasis accompanied by appropriate bone remodeling associated with ENPP1 function.