Evidence map›Paper›PMID 34454588›Full record

ArticleStem cell research & therapy2021

HDAC6 inactivates Runx2 promoter to block osteogenesis of bone marrow stromal cells in age-related bone loss of mice.

Chao Ma, Juan Gao, Jun Liang, Weixiang Dai, Zhenfei Wang, Mengjiao Xia, Tao Chen, Sen Huang, Jian Na, Long Xu and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

27 citing papers in PubMed, 36 citations in OpenAlex.

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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

13 authors at 2 institutions in 1 country.

Chao Ma *Department of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, 221009, Jiangsu, China.
Juan Gao *Department of Gynaecology and Obstetrics, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, 221009, Jiangsu, China.
Jun Liang *Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, 221009, Jiangsu, China.
Weixiang DaiDepartment of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, 221009, Jiangsu, China.
Zhenfei WangDepartment of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, 221009, Jiangsu, China.
Mengjiao XiaDepartment of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, 221009, Jiangsu, China.
Tao ChenDepartment of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, 221009, Jiangsu, China.
Sen HuangDepartment of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, 221009, Jiangsu, China.
Jian NaDepartment of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, 221009, Jiangsu, China.
Long XuDepartment of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, 221009, Jiangsu, China.
Shiming FengDepartment of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, 221009, Jiangsu, China.
Kerong DaiShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China.
Guangwang LiuDepartment of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, 221009, Jiangsu, China. guangwangliu@163.com.ORCID 0000-0002-6031-4568
Nanjing University of Chinese Medicine · CNShanghai Ninth People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSenile osteoporosis can cause bone fragility and increased risk for fractures and has been one of the most prevalent and severe diseases affecting the elderly population worldwidely. The underlying mechanisms are currently intensive areas of investigation. In age-related bone loss, decreased bone formation overweighs increased bone resorption. The molecular mechanisms underlying defective bone formation in age-related bone loss are not completely understood. In particular, the specific role of histone acetylation in age-related bone loss has not been examined thoroughly.

methodsWe employed 6- and 18-month-old mice to investigate the mechanisms of defective bone formation in age-related bone loss. Bone marrow stromal cells (BMSCs) were induced to undergo in vitro osteogenic differentiation. Chromatin immunoprecipitation (ChIP) was used to investigate the binding of histone deacetylases (HDACs) on Runx2 promoter in BMSCs. Luciferase reporter and transient transfection assay were employed to study Runx2 gene expression modulation by HDAC and androgen receptor (AR). siRNA and HDAC6 inhibitor, Tubastatin A, were used to inhibit HDAC6 in vitro. And systemic administration of Tubastatin A was used to block HDAC6 in vivo.

resultsAge-related trabecular bone loss was observed in 18-month-old mice compared with 6-month-old mice. In vitro osteogenic differentiation potential of BMSCs from 18-month-old mice was weaker than 6-month-old mice, in which there was Runx2 expression inactivation in BMSCs of 18-month-old mice compared with 6-month-old mice, which was attributable to HDAC6-mediated histone hypoacetylation in Runx2 promoter. There was competitive binding of HDAC6 and AR on Runx2 promoter to modulate Runx2 expression in BMSCs. More importantly, through siRNA- or specific inhibitor-mediated HDAC6 inhibition, we could activate Runx2 expression, rescue in vitro osteogenesis potential of BMSCs, and alleviate in vivo age-related bone loss of mice.

conclusionHDAC6 accumulation and histone hypoacetylation on Runx2 promoter contributed to the attenuation of in vitro osteogenic differentiation potential of BMSCs from aged mice. Through HDAC6 inhibition, we could activate Runx2 expression and osteogenic differentiation potential of BMSCs from aged mice and alleviate the age-related bone loss of aged mice. Our study will benefit not only for understanding the age-related bone loss, but also for finding new therapies to treat senile osteoporosis.

Indexed as

Mesenchymal Stem CellsOsteoporosisAgedAnimalsBone Marrow CellsCell DifferentiationCore Binding Factor Alpha 1 SubunitHistone Deacetylase 6HumansMiceOsteogenesisPromoter Regions, GeneticCore Binding Factor Alpha 1 SubunitHDAC6 protein, humanHistone Deacetylase 6RUNX2 protein, humanRunx2 protein, mouseAgingAndrogen receptorBone marrow stromal cellsHistone deacetylases 6OsteoporosisRunx2

Identifiers

PMID34454588
PMCPMC8403388
OpenAlexW3198694841

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.