Evidence map›Paper›PMID 39997596›Full record

ReviewJournal of functional biomaterials2025

Evaluating Bioassays for the Determination of Simvastatin's Osteogenic Activity: A Systematic Review.

Lara Steiner Back, Isabella Schönhofen Manso, Mariane Beatriz Sordi, Gabriel Leonardo Magrin, Águedo Aragonês, Ricardo de Souza Magini, Reinhard Gruber, Ariadne Cristiane Cabral Cruz

Abstract readReview
In one paragraph

Review in Journal of functional biomaterials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
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.

Lara Steiner BackPost-Graduation Program of Dentistry, Center for Education and Research on Dental Implants, Federal University of Santa Catarina, Florianópolis 88053-701, Brazil.ORCID 0000-0003-4887-026X
Isabella Schönhofen MansoPost-Graduation Program of Dentistry, Center for Education and Research on Dental Implants, Federal University of Santa Catarina, Florianópolis 88053-701, Brazil.
Mariane Beatriz SordiPost-Graduation Program of Dentistry, Center for Education and Research on Dental Implants, Federal University of Santa Catarina, Florianópolis 88053-701, Brazil.ORCID 0000-0001-7873-0765
Gabriel Leonardo MagrinPost-Graduation Program of Dentistry, Center for Education and Research on Dental Implants, Federal University of Santa Catarina, Florianópolis 88053-701, Brazil.ORCID 0000-0003-0724-0560
Águedo AragonêsPost-Graduation Program of Dentistry, Center for Education and Research on Dental Implants, Federal University of Santa Catarina, Florianópolis 88053-701, Brazil.
Ricardo de Souza MaginiPost-Graduation Program of Dentistry, Center for Education and Research on Dental Implants, Federal University of Santa Catarina, Florianópolis 88053-701, Brazil.
Reinhard GruberDepartment of Oral Biology, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria.
Ariadne Cristiane Cabral CruzPost-Graduation Program of Dentistry, Center for Education and Research on Dental Implants, Federal University of Santa Catarina, Florianópolis 88053-701, Brazil.ORCID 0000-0001-7306-4708

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveOsteogenic differentiation is a complex process, and its analysis requires several biomarkers. Allied with this, there are no standardized bioassays to monitor the activity of simvastatin in osteogenesis in vitro. Therefore, identifying the most efficient and sensitive bioassays may enhance the quality of in vitro studies, bridging the gap with in vivo findings, saving time and resources, and benefiting the community. This systematic review aimed to determine the most efficient bioassay for simvastatin's osteogenic activity in vitro, in terms of sensitivity. MATERIALS AND

methodsIn vitro studies evaluating undifferentiated mesenchymal cells treated with simvastatin were considered eligible. References were selected in a two-phase process. Electronic databases and the grey literature were screened up to September 2023. The Office of Health Assessment and Translation (OHAT) tool was used to assess the risk of bias. Certainty in cumulative evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Data were analyzed considering extracellular matrix mineralization, alkaline phosphatase, and the expression of potential target genes, such as bone morphogenetic protein-2 (BMP-2), collagen type I, Runt-related transcription factor 2, osterix, osteocalcin, and osteopontin.

resultsFourteen studies were included. A "probably low" or a "definitely low" risk of bias was assigned to the included studies. The simvastatin concentration ranged from 0.1 nM to 10 µM. Considering a minimum 4-fold increase, simvastatin caused robust mineralization of the extracellular matrix in four studies (4.0-, 4.4-, 5.0-, and 39.5-fold). Moreover, simvastatin substantially increased BMP-2 expression in mesenchymal cells in three studies (4-, 11-, and 19-fold).

conclusionTherefore, mineralization of the extracellular matrix and BMP-2 expression in mesenchymal cells are the most efficient bioassays for determining the osteogenic activity of simvastatin in vitro (high certainty level). These findings provide a standardized approach that can enhance the reliability and comparability of in vitro studies, bridging the gap with in vivo research and optimizing resources in the field of bone regeneration.

Indexed as

mesenchymal stromal cellmineralizationosteoblastosteogenesissimvastatin

Identifiers

PMID39997596
PMCPMC11855937

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.