Evidence map›Paper›PMID 29063674›Full record

ArticleJournal of cellular and molecular medicine2018

Indirect osteoblast differentiation by liposomal clodronate.

Emi Okada, Hidemi Nakata, Maiko Yamamoto, Shohei Kasugai, Shinji Kuroda

Open access · goldAbstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.5field-weighted citation impact, top 32% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Managing Mandibular Osteoradionecrosis.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2025
    Review
  3. Article
  4. Article
  5. Article
  6. RANKL and RANK in extracellular vesicles: surprising new players in bone remodeling.Extracellular vesicles and circulating nucleic acids · 2021
    Article
  7. Extracellular vesicle identification in tooth movement models.Orthodontics & craniofacial research · 2019
    Article
  8. Article
  9. 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

5 authors at 1 institution in 1 country.

Emi OkadaDepartment of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.ORCID 0000-0002-7187-6267
Hidemi NakataDepartment of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Maiko YamamotoDepartment of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Shohei KasugaiDepartment of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Shinji KurodaDepartment of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Tokyo Medical and Dental University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bisphosphonates impair function of osteoclasts and prevent bone resorption, the mechanism of which has been studied extensively. However, the possible effects of bisphosphonates on chondroblast differentiation and calcium deposition by osteoblasts have only been demonstrated recently. Moreover, cells from monocytic lineage are capable of stimulating osteoblast proliferation. Hence, susceptibility of osteoblasts to various factors requires further investigation. A primary culture of bone marrow-derived stromal cells was treated with liposomal clodronate (0.1, 0.5, or 1.0 mg/ml) or conditioned medium from liposomal clodronate. Liposomal clodronate (0.25 mg) was injected into mouse femur for in vivo experiments. The effects of liposomal clodronate were examined by alkaline phosphatase staining and/or activity assay, and real-time RT-PCR was used for studying the effect on osteogenic gene expression. Administration of liposomal clodronate to bone marrow-derived mesenchymal stromal cell culture enhanced alkaline phosphatase activity and mRNA levels of Runx2 and Dlx5. In addition, conditioned medium from liposomal clodronate also stimulated osteogenic characteristics similar to those of observed in vitro, and the number of exosomes in the conditioned medium was highest when pre-treated with liposomal clodronate. Western blot analysis revealed the presence of RANK proteins in exosomes collected from conditioned medium of liposomal clodronate. Identical observations were obtained in vivo, as liposomal clodronate-injected mouse femur showed increased alkaline phosphatase activity and Runx2 and Dlx5 mRNA expressions, even though the numbers of monocytes and macrophages were reduced. In conclusion, osteoblast differentiation was promoted via soluble RANK-containing exosomes in response to clodronates.

Indexed as

Alkaline PhosphataseAnimalsCell CountCell DifferentiationCells, CulturedCell SurvivalClodronic AcidCulture Media, ConditionedExosomesFemaleFemurGene Expression RegulationLiposomesMesenchymal Stem CellsMice, Inbred ICRMonocytesAlkaline PhosphataseClodronic AcidCulture Media, ConditionedLiposomesbisphosphonatesclodronate liposomesexosomesosteoblastssoluble RANK

Identifiers

PMID29063674
PMCPMC5783836
OpenAlexW2766887524

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.