Nov 13 2023

Cell Signal Transduction by Inorganic Phosphate and Inorganic Pyrophosphate

OHKURA Naoto, who belongs the Department of Dentistry, Niigata University Medical and Dental Hospital and is assistant professor (Postdoctoral researcher in Professor Nan Hatch's Laboratory of Pediatric Orthodontics, University of Michigan School of Dentistry at the time of the research), clarified that inorganic phosphate and pyrophosphate plays some crucial role in the cell signal transduction and phenotypic changes in intersphenoid synchondrosis (ISS¹) with organ culture of the skull base and immunohistological analysis, using conditional knockout mice in lack of tissue non-specific alkaline phosphatase (TNAP²) only in cranial neural crest cells³. They confirmed that TNAP play a crucial role in normal skull base development via chondrocytes, and that the mechanism may be also involved not only pyrophosphate but also proteins such as Sox9, PTHrP and IHH⁴. These research results were published in the online version of the International Journal of Molecular Sciences on October 20, 2023.

Key Points

• Transgenic Mice, which lacked tissue-nonspecific alkaline phosphatase (TNAP) deficiency (conditional knockout mice, hereafter cKO) only in cranial neural crest cells, showed abnormalities in chondrocyte proliferation, maturation, and apoptosis⁵.
• cKOs affected the signal transduction of Sox9, PTHrP and IHH in intersphenoid synchondrosis (ISS).
• TNAP was involved in the differentiation and stemness of cranial neural crest cells and played a role in the cell-autonomous role in neural crest cells.

[Term explanations]

1.Intersphenoid synchondrosis (ISS)
ISS is one of the growth areas at the skull base, and the growth ends at birth. The ISS is a synchondrodial joint that connects the sphenoid bone and the base of the occipital bone. The detailed figure is indicated below.

Figure: NanoCT analysis of mouse skull
ISS: Intersphenoidal symphysis,
SOS: Sphenooccipital symphysis
Bars indicate 200 µm.

2.Tissue non-specific alkaline phosphatase (TNAP)
TNAP is induced bone mineralization and change from hydrolyze inorganic pyrophosphate to inorganic phosphate.
Inorganic pyrophosphate: Inhibits matrix mineralization.
Inorganic phosphate: Substrate for hydroxyapatite formation.

3.Cranial neural crest cell
A pluripotent cell population derived from the neural crest cells of vertebrates. It can differentiate into various types of cells and contributes to the formation of craniofacial structures during embryonic development.

4.Sox9, PTHrP and IHH
All of these are the transcription factors involved in cartilage formation or the factors secreted from mesenchymal stem cells.

5.Apoptosis
Apoptosis is programmed cell death that is actively triggered to keep an individual in a better state.

Publication Details

Journal: International Journal of Molecular Sciences
Title: Cranial Neural Crest Specific Deletion of Alpl（TNAP）via P0-Cre Causes Abnormal Chondrocyte Maturation and Deficient Cranial Base Growth
Authors: Naoto Ohkura, Hwa Kyung Nam1, Fei Liu, Nan Hatch
DOI:10.3390/ijms242015401