Evidence map›Paper›PMID 38773377›Full record

ArticleMolecular medicine (Cambridge, Mass.)2024

Dickkopf-1 (DKK1) blockade mitigates osteogenesis imperfecta (OI) related bone disease.

Jih-Yang Ko, Feng-Sheng Wang, Wei-Shiung Lian, Fu-Shine Yang, Jeng-Wei Chen, Po-Hua Huang, Chin-Yi Liao, Shu-Jui Kuo

Abstract read
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Article in Molecular medicine (Cambridge, Mass.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

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0cells of the map it votes in
6citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Jih-Yang KoDepartment of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, 833401, Taiwan.
Feng-Sheng WangDepartment of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, 833401, Taiwan.
Wei-Shiung LianDepartment of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, 833401, Taiwan.
Fu-Shine YangDepartment of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, 833401, Taiwan.
Jeng-Wei ChenDepartment of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, 833401, Taiwan.
Po-Hua HuangDepartment of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, 833401, Taiwan.
Chin-Yi LiaoDepartment of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, 833401, Taiwan.
Shu-Jui KuoSchool of Medicine, China Medical University, Taichung City, 404328, Taiwan. b90401073@gmail.com.ORCID 0000-0002-2992-4608

Funding

China Medical University Hospital DMR-110-111China Medical University Hospital DMR-110-224China Medical University Hospital DMR-111-114China Medical University Hospital DMR-111-230China Medical University Hospital DMR-112-219Kaohsiung Chang Gung Memorial Hospital CRRPG8J0071~3Ministry of Science and Technology, Taiwan 108-2314-B-182A-073-Ministry of Science and Technology, Taiwan 109-2314-B-039-018-MY3Ministry of Science and Technology, Taiwan 109-2314-B-182A-168-Ministry of Science and Technology, Taiwan 110-2314-B-182A-149-Ministry of Science and Technology, Taiwan 111-2314-B-182A-055 -
6 · The paper itself

Abstract

backgroundThe current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI.

methodsWe analysed serum DKK1 levels and their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S).

resultsSignificant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = - 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = - 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p < 0.001), trabecular separation (p = 0.010), trabecular thickness (p = 0.001), trabecular number (p < 0.001), and cortical thickness (p < 0.001) in OI mice. DKK1-AS enhanced the transcription of collagen 1α1, osteocalcin, runx2, and osterix in BMSC from OI mice (all p < 0.001), resulting in a higher von Kossa-stained matrix area (p < 0.001) in ex vivo osteogenesis assays. DKK1-AS also reduced osteoclast numbers (p < 0.001), increased β-catenin and T-cell factor 4 immunostaining reactivity (both p < 0.001), enhanced mineral apposition rate and bone formation rate per bone surface (both p < 0.001), and decreased osteoclast area (p < 0.001) in OI mice. DKK1-AS upregulated osteoprotegerin and downregulated nuclear factor-kappa B ligand transcription (both p < 0.001). Bone tissues from OI mice treated with DKK1-AS exhibited significantly higher breaking force compared to untreated OI mice (p < 0.001).

conclusionsOur study elucidates that DKK1-AS has the capability to enhance bone mechanical properties, restore the transcription of osteogenic genes, promote osteogenesis, and inhibit osteoclastogenesis in OI mice.

Indexed as

Disease Models, AnimalIntercellular Signaling Peptides and ProteinsOsteogenesis ImperfectaAnimalsBone DensityFemaleHumansMaleMesenchymal Stem CellsMiceOsteogenesisDKK1 protein, humanDkk1 protein, mouseIntercellular Signaling Peptides and ProteinsDickkopf-1 (DKK1)Nuclear factor-kappa B ligand (RANKL)Osteogenesis imperfecta (OI)Osteoprotegerin (OPG)T-cell factor 4 (TCF4)Wnt3aβ-Catenin

Identifiers

PMID38773377
PMCPMC11106911

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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.