Evidence map›Paper›PMID 25336648›Full record

ArticleThe Journal of biological chemistry2015

PTH1-34 blocks radiation-induced osteoblast apoptosis by enhancing DNA repair through canonical Wnt pathway.

Abhishek Chandra, Tiao Lin, Ji Zhu, Wei Tong, Yanying Huo, Haoruo Jia, Yejia Zhang, X Sherry Liu, Keith Cengel, Bing Xia and 1 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

  1. Pooled it
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  16. Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics.International journal of molecular sciences · 2021
    Review
  17. Radiotherapy-induced bone deterioration is exacerbated in diabetic rats treated with streptozotocin.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2021
    Article
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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 5 institutions in 2 countries.

Abhishek ChandraFrom the Department of Orthopaedic Surgery.
Tiao LinFrom the Department of Orthopaedic Surgery, the Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Ji ZhuFrom the Department of Orthopaedic Surgery.
Wei TongFrom the Department of Orthopaedic Surgery, the Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 Hubei, China.
Yanying Huothe Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick, New Jersey 08903, and.
Haoruo JiaFrom the Department of Orthopaedic Surgery.
Yejia ZhangDepartments of Physical Medicine & Rehabilitation and Orthopedic Surgery, and the Translational Musculoskeletal Research Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania 19104.
X Sherry LiuFrom the Department of Orthopaedic Surgery.
Keith CengelDepartment of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Bing Xiathe Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick, New Jersey 08903, and.
Ling QinFrom the Department of Orthopaedic Surgery, qinling@mail.med.upenn.edu.
Rutgers, The State University of New Jersey · USHuazhong University of Science and Technology · CNSecond Affiliated Hospital of Zhejiang University · CNUniversity of Pennsylvania · USVeterans Health Administration · US

Funding

The Role of Hyaluronic Acid Receptors in Tendon HealingP30AR050950 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI PIGNOLO, ROBERT JOHN · 2006 to 2015
$6.2M
Role of PALB2 in the DNA Damage Response and Cancer SuppressionR01CA138804 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI XIA, BING · 2009 to 2024
$5.5M
Role of EGFR signaling in bone formation and the anabolic actions of PTHR01DK095803 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI QIN, LING · 2013 to 2017
$1.7M
NCI NIH HHS R01 CA138804NCI NIH HHS R01CA138804NIAMS NIH HHS P30 AR050950NIDDK NIH HHS R01 DK095803NIDDK NIH HHS R01DK095803
6 · The paper itself

Abstract

Focal radiotherapy for cancer patients has detrimental effects on bones within the radiation field and the primary clinical signs of bone damage include the loss of functional osteoblasts. We reported previously that daily injection of parathyroid hormone (PTH, 1-34) alleviates radiation-induced osteopenia in a preclinical radiotherapy model by improving osteoblast survival. To elucidate the molecular mechanisms, we irradiated osteoblastic UMR 106-01 cells and calvarial organ culture and demonstrated an anti-apoptosis effect of PTH1-34 on these cultures. Inhibitor assay indicated that PTH exerts its radioprotective action mainly through protein kinase A/β-catenin pathway. γ-H2AX foci staining and comet assay revealed that PTH efficiently promotes the repair of DNA double strand breaks (DSBs) in irradiated osteoblasts via activating the β-catenin pathway. Interestingly, Wnt3a alone also blocked cell death and accelerated DNA repair in primary osteoprogenitors, osteoblastic and osteocytic cells after radiation through the canonical signaling. Further investigations revealed that both Wnt3a and PTH increase the amount of Ku70, a core protein for initiating the assembly of DSB repair machinery, in osteoblasts after radiation. Moreover, down-regulation of Ku70 by siRNA abrogated the prosurvival effect of PTH and Wnt3a on irradiated osteoblasts. In summary, our results identify a novel role of PTH and canonical Wnt signaling in regulating DSB repair machinery and apoptosis in osteoblasts and shed light on using PTH1-34 or Wnt agonist as possible therapy for radiation-induced osteoporosis.

Indexed as

AnimalsAnimals, NewbornAntigens, NuclearApoptosisbeta CateninCell DifferentiationCell Line, TumorCyclic AMP-Dependent Protein KinasesDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA RepairGene Expression RegulationKu AutoantigenOsteoblastsOsteocytesParathyroid HormoneAntigens, Nuclearbeta CateninCtnnb1 protein, ratCyclic AMP-Dependent Protein KinasesDNA-Binding ProteinsKu AutoantigenParathyroid HormoneRadiation-Protective AgentsRecombinant ProteinsWnt3A ProteinXrcc6 protein, ratApoptosisDNA RepairIonizing RadiationOsteoblastParathyroid HormoneWnt Pathway

Identifiers

PMID25336648
PMCPMC4281718
OpenAlexW1970795454

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.