Evidence map›Paper›PMID 41348313›Full record

ArticleBiochemical genetics2026

Knockdown of MEPE Promotes Cranial Defect Repair and Activates the cAMP/PKA Signaling Pathway.

Kai Hong, Jianping Wu, Xinwang Zhi, Weizhe Shi, Hongwen Xu

Abstract read
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In one paragraph

Article in Biochemical genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

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4 · The record

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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

5 authors.

Kai Hong *Department of Pediatric Orthopedics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9, Jinsui Road, Tianhe District, Guangzhou, 510000, Guangdong, China.
Jianping Wu *Department of Pediatric Orthopedics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9, Jinsui Road, Tianhe District, Guangzhou, 510000, Guangdong, China.
Xinwang ZhiDepartment of Pediatric Orthopedics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9, Jinsui Road, Tianhe District, Guangzhou, 510000, Guangdong, China.
Weizhe ShiDepartment of Pediatric Orthopedics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9, Jinsui Road, Tianhe District, Guangzhou, 510000, Guangdong, China.
Hongwen XuDepartment of Pediatric Orthopedics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9, Jinsui Road, Tianhe District, Guangzhou, 510000, Guangdong, China. gzfezxgk@163.com.

Funding

Guangzhou Municipal Science and Technology Bureau 2023 Annual Basic and Applied Basic Research Special Project SL2022A04J00806
6 · The paper itself

Abstract

Cranial defect repair remains a clinical challenge in current surgical practice. Matrix extracellular phosphoglycoprotein (MEPE) plays a role in mineralization, but its specific mechanism in calvarial bone repair, particularly concerning oxidative stress, remains unclear. Bioinformatics analysis identified hub genes and pathways from the calvarial defect dataset GSE20980 using differentially expressed genes screening (p < 0.05, |log2Foldchange|≥3) and weighted gene co-expression network analysis. In vivo, a rat critical-sized calvarial defect (CSD) model was established. MEPE was knocked down via lentiviral siRNA delivery. Bone repair was assessed 8 weeks post-surgery using micro-computed tomography (bone volume/total volume [BV/TV] and trabecular number [Tb.N]), histology (hematoxylin-eosin staining and tartrate-resistant acid phosphatase staining). Enzyme-linked immunosorbent assay was performed to evaluate levels of inflammatory cytokines and oxidative stress indicators. MEPE-associated pathways were screened, and the protein levels were measured by western blot. Bioinformatics analyses identified MEPE as a key upregulated hub gene in bone defects. In vivo, MEPE expression was significantly elevated in CSD rats. MEPE knockdown enhanced bone repair (increased BV/TV and Tb.N), and promoted bone formation and angiogenesis. Furthermore, knockdown of MEPE reduced inflammation (decreased tumor necrosis factor alpha, interleukin 6, interleukin-1β), reactive oxygen species level, increased antioxidants (elevated catalase, glutathione, superoxide dismutase) and upregulated osteogenic markers (runt-related transcription factor 2, osteocalcin, alkaline phosphatase). Bioinformatics analysis of intersecting genes implicated the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway as the downstream pathway of MEPE. Mechanistically, MEPE knockdown reversed CSD-induced suppression of cAMP and PKA protein expression. MEPE knockdown promotes calvarial bone repair by mitigating oxidative stress, reducing inflammation, enhancing osteogenesis, and activating the cAMP/PKA signaling pathway, representing a potential therapeutic target for bone regeneration.

Indexed as

Bone RegenerationCyclic AMPCyclic AMP-Dependent Protein KinasesExtracellular Matrix ProteinsGlycoproteinsSignal TransductionSkullAnimalsGene Knockdown TechniquesMaleOsteogenesisOxidative StressRatsRats, Sprague-DawleyCyclic AMPCyclic AMP-Dependent Protein KinasesExtracellular Matrix ProteinsGlycoproteinsBioinformatics analysisCalvarial bone repairCAMP/PKA signaling pathwayMEPE

Identifiers

PMID41348313

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.