Osteoblast Autonomous Pi Regulation via Pit1 Plays a Role in Bone Mineralization

Yoshiko, Yuji; Candeliere, G. Antonio; Maeda, Norihiko; Aubin, Jane E.

doi:10.1128/mcb.00104-07

Cited by 140Alkaline Phosphatase Research StudiesParathyroid Disorders and TreatmentsBone Metabolism and Diseases

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Osteoblast Autonomous Pi Regulation via Pit1 Plays a Role in Bone Mineralization

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Yoshiko, Yuji, Candeliere, G. Antonio, Maeda, Norihiko, Aubin, Jane E.·2007·Molecular and Cellular Biology

DOI 10.1128/mcb.00104-07PMC PMC1900051

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Abstract

The complex pathogenesis of mineralization defects seen in inherited and/or acquired hypophosphatemic disorders suggests that local inorganic phosphate (P(i)) regulation by osteoblasts may be a rate-limiting step in physiological bone mineralization. To test whether an osteoblast autonomous phosphate regulatory system regulates mineralization, we manipulated well-established in vivo and in vitro models to study mineralization stages separately from cellular proliferation/differentiation stages of osteogenesis. Foscarnet, an inhibitor of NaP(i) transport, blocked mineralization of osteoid formation in osteoblast cultures and local mineralization after injection over the calvariae of newborn rats. Mineralization was also down- and upregulated, respectively, with under- and overexpression of the type III NaP(i) transporter Pit1 in osteoblast cultures. Among molecules expressed in osteoblasts and known to be related to P(i) handling, stanniocalcin 1 was identified as an early response gene after foscarnet treatment; it was also regulated by extracellular P(i), and itself increased Pit1 accumulation in both osteoblast cultures and in vivo. These results provide new insights into the functional role of osteoblast autonomous P(i) handling in normal bone mineralization and the abnormalities seen in skeletal tissue in hypophosphatemic disorders.

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Mineralization of bone matrix takes place in two phases: the vesicular and the fibrillar phases.
“Thereafter, mineralization of bone matrix takes place into two phases: the vesicular and the fibrillar phases [40, 41].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [41]

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Authors: Yoshiko, Y., Candeliere, G. A., Maeda, N., & Aubin, J. E.
Affiliations: Hiroshima University (JP)
University of Toronto (CA)
Corresponding author: Yoshiko, Yuji
Aubin, Jane E.
ORCID: Aubin, Jane E.
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 2007-06-01
Volume: 27
Issue: 12
Pages: 4465-4474
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.00104-07
PMC: PMC1900051
OpenAlex: W2145172006
Cited by: 140
References: 47
Citations by year: 2026: 1 · 2025: 8 · 2024: 4 · 2023: 8 · 2022: 4 · 2021: 2 · 2020: 7 · 2019: 9 · 2018: 11 · 2017: 8 · 2016: 8 · 2015: 5 · 2014: 3 · 2013: 13 · 2012: 12
FWCI: 6.36
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Institutes of Health Research
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords: bone mineralization, osteoblasts, Pit-1, foscarnet, stanniocalcin-1, hypophosphatemia, osteoid formation, phosphate transporters, extracellular phosphate
MeSH terms: Animals, Calcification, Physiologic, Cells, Cultured, Gene Expression Regulation, Glycerophosphates, Glycoproteins, Humans, Models, Biological, Osteoblasts, Phosphorus, Osteosarcoma, Skull, 3T3 Cells, Rats, Wistar, Foscarnet, Sodium-Phosphate Cotransporter Proteins, Type III, Transcription Factor Pit-1, Mice, Rats

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Osteoblast Autonomous Pi Regulation via Pit1 Plays a Role in Bone Mineralization

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