Evidence map›Paper›PMID 27016531›Full record

ArticleJournal of dental research2016

Role of PHOSPHO1 in Periodontal Development and Function.

L E Zweifler, M Ao, M Yadav, P Kuss, S Narisawa, T N Kolli, H F Wimer, C Farquharson, M J Somerman, J L Millán and 1 more

Open access · greenAbstract read
In one paragraph

Article in Journal of dental research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 26 citations in OpenAlex.

  1. A spatially organizedScience advances · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 2 countries.

L E ZweiflerDivision of Biosciences, College of Dentistry, Ohio State University, Columbus, OH, USA.
M AoNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
M YadavSanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
P KussSanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
S NarisawaSanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
T N KolliDivision of Biosciences, College of Dentistry, Ohio State University, Columbus, OH, USA.
H F WimerDepartment of Vertebrate Zoology, National Museum of Natural History, Smithsonian Institution, Washington, DC, USA National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
C FarquharsonRoslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UK.
M J SomermanNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
J L MillánSanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
B L FosterDivision of Biosciences, College of Dentistry, Ohio State University, Columbus, OH, USA foster.1004@osu.edu.
Discovery Institute · USThe Ohio State University · USNational Institute of Arthritis and Musculoskeletal and Skin Diseases · USRoslin Institute · GBSanford Burnham Prebys Medical Discovery Institute · USSmithsonian Institution · US

Funding

NIAMS Light Imaging FacilityZICAR041186 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI RANDAZZO, DAVIDE · 2010 to 2025
$18.2M
Tissue Engineering and RegenerationT32DE007057 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID H. KOHN · 1985 to 2026
$17.3M
MOLECULAR PATHOGENESIS/TREATMENT OF HYPOPHOSPHATASIAR01DE012889 · NIDCR · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MILLAN, JOSE LUIS · 1999 to 2020
$9.2M
Laboratory of Oral Connective Tissue BiologyZIAAR041196 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI SOMERMAN, MARTHA · 2013 to 2021
$8.9M
Mechanisms of initiation of skeletal mineralizationR01AR053102 · NIAMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MILLAN, JOSE LUIS · 2006 to 2015
$3.8M
Extracellular Matrix and Phosphate/Pyrophosphate Metabolism in Cementum FormationR00AR066110 · NIAMS · OHIO STATE UNIVERSITY · PI FOSTER, BRIAN LEE · 2015 to 2017
$747k
Biotechnology and Biological Sciences Research Council BB/J004316/1NIAMS NIH HHS R00 AR066110NIAMS NIH HHS R01 AR053102NIDCR NIH HHS R01 DE012889NIDCR NIH HHS T32 DE007057
6 · The paper itself

Abstract

The tooth root and periodontal apparatus, including the acellular and cellular cementum, periodontal ligament (PDL), and alveolar bone, are critical for tooth function. Cementum and bone mineralization is regulated by factors including enzymes and extracellular matrix proteins that promote or inhibit hydroxyapatite crystal growth. Orphan Phosphatase 1 (Phospho1, PHOSPHO1) is a phosphatase expressed by chondrocytes, osteoblasts, and odontoblasts that functions in skeletal and dentin mineralization by initiating deposition of hydroxyapatite inside membrane-limited matrix vesicles. The role of PHOSPHO1 in periodontal formation remains unknown and we aimed to determine its functional importance in these tissues. We hypothesized that the enzyme would regulate proper mineralization of the periodontal apparatus. Spatiotemporal expression of PHOSPHO1 was mapped during periodontal development, and Phospho1(-/-) mice were analyzed using histology, immunohistochemistry, in situ hybridization, radiography, and micro-computed tomography. The Phospho1 gene and PHOSPHO1 protein were expressed by active alveolar bone osteoblasts and cementoblasts during cellular cementum formation. In Phospho1(-/-) mice, acellular cementum formation and mineralization were unaffected, whereas cellular cementum deposition increased although it displayed delayed mineralization and cementoid. Phospho1(-/-) mice featured disturbances in alveolar bone mineralization, shown by accumulation of unmineralized osteoid matrix and interglobular patterns of protein deposition. Parallel to other skeletal sites, deposition of mineral-regulating protein osteopontin (OPN) was increased in alveolar bone in Phospho1(-/-) mice. In contrast to the skeleton, genetic ablation of Spp1, the gene encoding OPN, did not ameliorate dentoalveolar defects in Phospho1(-/-) mice. Despite alveolar bone mineralization defects, periodontal attachment and function appeared undisturbed in Phospho1(-/-) mice, with normal PDL architecture and no evidence of bone loss over time. This study highlights the role of PHOSPHO1 in mineralization of alveolar bone and cellular cementum, further revealing that acellular cementum formation is not substantially regulated by PHOSPHO1 and likely does not rely on matrix vesicle-mediated initiation of mineralization.

Indexed as

Alveolar ProcessAnimalsCalcification, PhysiologicDental CementumDurapatiteGene ExpressionIn Situ HybridizationMiceMice, Inbred C57BLOsteoblastsPeriodontal LigamentPeriodontiumPhosphoric Monoester HydrolasesX-Ray MicrotomographyDurapatitePHOSPHO1 protein, mousePhosphoric Monoester Hydrolasesbonecementumdentinextracellular matrixperiodontal ligamentphysiologic calcification

Identifiers

PMID27016531
PMCPMC4914864
OpenAlexW2304856606

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.