Evidence map›Paper›PMID 37898986›Full record

ArticleJournal of bone and mineral metabolism2023

Sirtuin 6 ameliorates arthritis through modulating cyclic AMP-responsive element binding protein/CCN1/cyclooxygenase 2 pathway in osteoblasts.

Sze-Kwan Lin, Han-Wei Wang, Chia-Tung Shun, Cheng-Ning Yang, Chi-Yuan Hong, Eddie Hsiang-Hua Lai, Shih-Jung Cheng, Mu-Hsiung Chen, Hsiang Yang, Hung-Ying Lin and 2 more

Abstract read
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In one paragraph

Article in Journal of bone and mineral metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.4field-weighted citation impact, top 39% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Research advances on silence information regulator 6 as a potential therapeutic target for bone regeneration and repair.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024
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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

12 authors at 2 institutions in 1 country.

Sze-Kwan LinDepartment of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
Han-Wei WangDepartment of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
Chia-Tung ShunDepartment of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Cheng-Ning YangDepartment of Dentistry, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chi-Yuan HongDepartment of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
Eddie Hsiang-Hua LaiDepartment of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
Shih-Jung ChengDepartment of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
Mu-Hsiung ChenDepartment of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
Hsiang YangDepartment of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
Hung-Ying LinDepartment of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
Fang-Yu WuDepartment of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
Sang-Heng KokDepartment of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan. shkok@ntu.edu.tw.ORCID http://orcid.org/0000-0001-6445-8852
National Taiwan University · TWNational Taiwan University Hospital · TW

Funding

National Science and Technology Council MOST 109-2314-B-002-034-MY3National Science and Technology Council MOST 111-2314-B-002-113National Taiwan University Hospital NTUH 109-S4494National Taiwan University Hospital NTUH 109-S4746National Taiwan University Hospital NTUH 110-S4841National Taiwan University Hospital NTUH 111-S0140
6 · The paper itself

Abstract

introductionCCN1 is an immediate-early gene product pivotal for arthritis progression. We have previously shown that sirtuin 6 (SIRT6) inhibited hypoxia-induced CCN1 expression in osteoblasts. Herein we examined the contribution of cyclic AMP-responsive element binding protein (CREB)/CRE to this suppressive action and the influence of CCN1 on cyclooxygenase (COX) 2 synthesis. MATERIALS AND

methodsMC3T3-E1 murine osteoblasts were cultured under normoxia (21% oxygen) or hypoxia (2% oxygen). Expressions of CCN1, phospho-CREB (Ser133), COX2 and relevant kinases were assessed by Western blot. SIRT6 was overexpressed in cultured osteoblasts and arthritic joints by a lentiviral-based technique. Activities of CCN1 gene promoter constructs were examined by luciferase reporter assay. Interaction between CREB and CCN1 promoter was assessed by chromatin immunoprecipitation (ChIP). Collagen-induced arthritis (CIA) was established in 20 rats to evaluate the effects of SIRT6 therapy on osteoblastic expressions of phospho-CREB, CCN1 and COX2.

resultsSIRT6 suppressed hypoxia-enhanced CCN1 expression and CREB phosphorylation. Attenuation of calcium/calmodulin-dependent protein kinase II (CaMKII) may be responsible for SIRT6-induced CREB inhibition. CRE at - 286 bp upstream of the ATG start codon was essential for CCN1 expression under hypoxia and SIRT6 reduced hypoxia-stimulated CREB/CRE interaction. Forced expression of CREB rescued SIRT6-suppressed CCN1 synthesis. CCN1 induced COX2 expression in osteoblasts. In rat CIA, the therapeutic effect of SIRT6 was accompanied by decreases in osteoblastic expressions of phospho-CREB, CCN1 and COX2.

conclusionOur study indicated that the benefits of SIRT6 to inflammatory arthritis and bone resorption are at least partially derived from its modulation of CREB/CCN1/COX2 pathway in osteoblasts.

Indexed as

Arthritis, ExperimentalSirtuinsAnimalsCyclic AMPCyclic AMP Response Element-Binding ProteinCyclooxygenase 2HypoxiaMiceOsteoblastsOxygenPhosphorylationRatsCyclic AMPCyclic AMP Response Element-Binding ProteinCyclooxygenase 2OxygenSirtuinsCCN1Collagen-induced arthritisCyclic AMP-responsive element binding proteinCyclooxygenase 2Sirtuin 6

Identifiers

PMID37898986
OpenAlexW4388008584

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.