Evidence map›Paper›PMID 22014174›Full record

ArticleJournal of periodontology2012

Correction of hypophosphatasia-associated mineralization deficiencies in vitro by phosphate/pyrophosphate modulation in periodontal ligament cells.

Thaisângela L Rodrigues, Brian L Foster, Karina G Silverio, Luciane Martins, Marcio Z Casati, Enilson A Sallum, Martha J Somerman, Francisco H Nociti

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of periodontology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

6 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. The rachitic tooth.Endocrine reviews · 2014
    Review
  3. Article
  4. Article
  5. Article
  6. Review
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

8 authors at 1 institution in 1 country.

Thaisângela L RodriguesDepartment of Prosthodontics and Periodontics, Campinas State University, Piracicaba, São Paulo, Brazil.
Brian L Foster
Karina G Silverio
Luciane Martins
Marcio Z Casati
Enilson A Sallum
Martha J Somerman
Francisco H Nociti
Universidade Estadual de Campinas (UNICAMP) · BR

Funding

Laboratory of Oral Connective Tissue BiologyZIAAR041196 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI SOMERMAN, MARTHA · 2013 to 2021
$8.9M
Key Modulators of CementogenesisR01DE015109 · NIDCR · UNIVERSITY OF WASHINGTON · PI POPOWICS, TRACY E · 2003 to 2011
$2.9M
Key Modulators of CementogenesisR56DE015109 · NIDCR · UNIVERSITY OF WASHINGTON · PI SOMERMAN, MARTHA J · 2007 to 2007
$390k
Phosphate Modulation of Dental TissuesR03TW007590 · FIC · UNIVERSITY OF WASHINGTON · PI SOMERMAN, MARTHA J · 2006 to 2008
$116k
FIC NIH HHS 5R03TW007590-03FIC NIH HHS R03 TW007590NIDCR NIH HHS DE15109NIDCR NIH HHS R01 DE015109NIDCR NIH HHS R56 DE015109
6 · The paper itself

Abstract

backgroundMutations in the liver/bone/kidney alkaline phosphatase (ALPL) gene in hypophosphatasia (HPP) reduce the function of tissue non-specific alkaline phosphatase (ALP), resulting in increased pyrophosphate (PP(i)) and a severe deficiency in acellular cementum. We hypothesize that exogenous phosphate (P(i)) would rescue the in vitro mineralization capacity of periodontal ligament (PDL) cells harvested from HPP-diagnosed patients, by correcting the P(i)/PP(i) ratio and modulating expression of genes involved with P(i)/PP(i) metabolism.

methodsEx vivo and in vitro analyses were used to identify mechanisms involved in HPP-associated PDL/tooth root deficiencies. Constitutive expression of PP(i)-associated genes was contrasted in PDL versus pulp tissues obtained from healthy individuals. Primary PDL cell cultures from patients with HPP (monozygotic twin males) were established to assay ALP activity, in vitro mineralization, and gene expression. Exogenous P(i) was provided to correct the P(i)/PP(i) ratio.

resultsPDL tissues obtained from healthy individuals featured higher basal expression of key PP(i) regulators, genes ALPL, progressive ankylosis protein (ANKH), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), versus paired pulp tissues. A novel ALPL mutation was identified in the twin patients with HPP enrolled in this study. Compared to controls, HPP-PDL cells exhibited significantly reduced ALP and mineralizing capacity, which were rescued by addition of 1 mM P(i). Dysregulated expression of PP(i) regulatory genes ALPL, ANKH, and ENPP1 was also corrected by adding P(i), although other matrix markers evaluated in our study remained downregulated.

conclusionThese findings underscore the importance of controlling the P(i)/PP(i) ratio toward development of a functional periodontal apparatus and support P(i)/PP(i) imbalance as the etiology of HPP-associated cementum defects.

Indexed as

AdolescentAlkaline PhosphataseCase-Control StudiesDental CementumDental PulpDiphosphatesDiseases in TwinsDNA Mutational AnalysisFemaleGene Expression ProfilingGene Expression Regulation, EnzymologicHumansHypophosphatasiaMalePeriodontal LigamentPhosphatesAlkaline PhosphataseALPL protein, humanANKH protein, humanDiphosphatesdiphosphoric acidectonucleotide pyrophosphatase phosphodiesterase 1PhosphatesPhosphate Transport ProteinsPhosphoric Diester HydrolasesPyrophosphatases

Identifiers

PMID22014174
PMCPMC3871996
OpenAlexW2071178698

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.