Evidence map›Paper›PMID 29600563›Full record

ArticleJournal of cellular physiology2018

Alendronate induces osteoclast precursor apoptosis via peroxisomal dysfunction mediated ER stress.

Ning Ding, Chuan Liu, Li Yao, Yun Bai, Peng Cheng, Zhilin Li, Keyu Luo, Tieniu Mei, Jianhua Li, Junchao Xing and 5 more

Abstract read
In one paragraph

Article in Journal of cellular physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 19% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Stigmasterol, a Major Component ofJournal of musculoskeletal & neuronal interactions · 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

15 authors at 3 institutions in 1 country.

Ning DingDepartment of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Chuan LiuDepartment of Biomedical Materials Science, Third Military Medical University (Army Medical University), Chongqing, China.
Li YaoDepartment of Urology, The Army General Hospital, Beijing, China.
Yun BaiDepartment of Biomedical Materials Science, Third Military Medical University (Army Medical University), Chongqing, China.
Peng ChengDepartment of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Zhilin LiDepartment of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Keyu LuoDepartment of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Tieniu MeiDepartment of Surgery, Shigatse Branch of Xinqiao Hospital, The Third Military Medical University (Army Medical University), Shigatse, China.
Jianhua LiDepartment of Orthopedics, The 88 Hospital of PLA, Taian, China.
Junchao XingDepartment of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Xiaoliang GaoDepartment of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Qinyu MaDepartment of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Jianzhong XuDepartment of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Fei LuoDepartment of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Ce DouDepartment of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.ORCID http://orcid.org/0000-0002-6983-6354
Army Medical University · CN82th Hospital of Pla · CNThe Military General Hospital of Beijing PLA · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nitrogen-containing bisphosphonates including alendronate (ALN) are the current first line antiresorptive drug in treating osteoporosis. In our study, we found that ALN administration impaired the secretion of platelet derived growth factor-BB (PDGF-BB), the most important angiogenic cytokines produced by preosteoclast (POC), in both sham and ovariectomized (OVX) mice. To further understand this phenomenon, we induced bone marrow macrophages (BMMs) to POCs in vitro and detected the effects of ALN particularly in POCs. The proapoptotic effect of ALN in POCs was confirmed by flow cytometry. On the molecular level, we found that farnesyl diphosphate synthase (FDPS) inhibition of ALN led to peroxisomal dysfunction and up regulation of cytoprotective protein glucose-regulated protein (GRP) 78. Peroxisomal dysfunction further induced endoplasmic reticulum (ER) stress in POCs and finally resulted in cell apoptosis marked by reduced expression of B-cell lymphoma 2 (Bcl-2) and increased expressions of CCAAT/enhancer binding protein homologous protein (CHOP), Bcl2 associated X (Bax), and cleaved caspase-3. We concluded that ALN has no selectivity in inhibiting POC and mature osteoclast. For POCs, ALN inhibition of FDPS leads to peroxisomal dysfunction, which further mediates ER stress and finally causes cell apoptosis. Considering that decreased angiogenesis is also an important issue in treating osteoporosis, how to preserve pro-angiogenic POCs while depleting mature osteoclasts is a problem worthy to be solved.

Indexed as

AlendronateAnimalsApoptosisBecaplerminCell CountCell Cycle CheckpointsEndoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressFemaleHeat-Shock ProteinsMice, Inbred C57BLOsteoclastsOsteoporosisOvariectomyPeroxisomesUp-RegulationAlendronateBecaplerminEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsalendronateapoptosisER stressosteoclastperoxisome

Identifiers

PMID29600563
PMCPMC13482122
OpenAlexW2794961721

What OpenQuestion holds

Textmetadata
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.