Evidence mapPaperPMID 40160965Full record

ArticleDrug design, development and therapy2025

MK-4 Ameliorates Diabetic Osteoporosis in Angiogenesis-Dependent Bone Formation by Promoting Mitophagy in Endothelial Cells.

Fan Ding, Weidong Zhang, Ting Liu, Xing Rong, Yajun Cui, Lingxiao Meng, Luxu Wang, Bo Liu, Minqi Li

Abstract read
In one paragraph

Article in Drug design, development and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
field-weighted citation impact
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

8 citing papers in PubMed.

  1. Menaquinone-4 protects CD8Science China. Life sciences · 2026
    Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Vitamin KDrug design, development and therapy · 2025
    Article
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

9 authors.

Fan DingDepartment of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People's Republic of China.
Weidong ZhangDepartment of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People's Republic of China.
Ting LiuDepartment of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People's Republic of China.ORCID 0009-0008-8614-1213
Xing RongDepartment of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People's Republic of China.
Yajun CuiDepartment of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People's Republic of China.ORCID 0009-0004-7851-173X
Lingxiao MengDepartment of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People's Republic of China.
Luxu WangDepartment of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People's Republic of China.
Bo LiuSchool of Clinical Medicine, Jining Medical University, Jining, People's Republic of China.
Minqi LiDepartment of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People's Republic of China.ORCID 0000-0001-9980-1382

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Diabetic osteoporosis (DOP), one of the usual complications in diabetic patients, poses a significant threat to bone health. Type H vessels in metaphysis and medial cortical bone are associated with osteogenesis. As a form of Vitamin K Methods: High fat diet (HDF) feeding and streptozotocin (STZ) injection were applied to establish a mouse model of type 2 diabetic osteoporosis (T2DOP). Micro-CT, Masson staining, HE staining and IHC staining were applied to observe bone mass and the osteoblastic ability of osteoblasts. Tissue immunofluorescence (IF) staining and flow cytometry were employed to assess alteration of type H blood vessels. In vitro, to evaluate the functional level and mitophagy of ECs under high glucose conditions, wound healing assay, tube formation assay, EdU assay and IF were employed. Osteogenic differentiation ability in vitro was evaluated by ALP staining, AR staining, Western blot and RT-qPCR. Results: MK-4 alleviated type H vessel injury and angiogenesis-dependent osteogenesis in DOP mice, thereby maintaining the bone mass. The vitro results showed that MK-4 could mitigate the dysfunction of ECs subjected to HG treatment, and further facilitate the osteogenic differentiation of MC3T3-E1 cells. Moreover, mechanism exploration found that PINK1/Parkin-mediated mitophagy was required for the impact of MK-4 on ECs. Meanwhile, ERK signal pathway is necessary for the improvement of MK-4 in PINK1/Parkin-mediated mitophagy. Conclusion: MK-4 is capable of alleviating the PINK1/Parkin-mediated mitophagy of ECs via the ERK pathway, thereby facilitating angiogenesis-dependent bone formation and further ameliorating DOP.

Indexed as

Diabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Endothelial CellsMitophagyOsteogenesisOsteoporosisVitamin K 2AngiogenesisAnimalsCells, CulturedDiet, High-FatDisease Models, AnimalDose-Response Relationship, DrugHumansMaleMicemenatetrenoneStreptozocinVitamin K 2angiogenesis-dependent osteogenesisdiabetic osteoporosisMenaquinone-4PINK1/Parkin-dependent mitophagytype H vessels

Identifiers

PMID40160965
PMCPMC11954476

What Socratic holds

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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 Socratic graph.