NLRC5 Deficiency Delays Bone Healing by Inhibiting Osteogenic Differentiation of Bone Marrow-Derived Stem Cells and Altering the Immune Microenvironment.

Peiying Lyu, Jianru Liu, Yuanbo Wang, Wenyi Liu, Jinsheng Zhong, Xiangying Ouyang

Abstract read

In one paragraph

Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

6 authors.

Peiying LyuDepartment of Periodontology, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China.ORCID 0000-0002-4149-6335

Jianru LiuDepartment of Periodontology, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China.

Yuanbo WangDepartment of Periodontology, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China.

Wenyi LiuDepartment of Periodontology, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China.

Jinsheng ZhongDepartment of Periodontology, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China.

Xiangying OuyangDepartment of Periodontology, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China.ORCID 0000-0003-3703-0847

Funding

National Key Research and Development Program of China 2023YFC2506301-2/3

6 · The paper itself

Abstract

Modulating the immune microenvironment has become an emerging strategy for promoting functional bone regeneration, identifying key therapeutic targets remains challenging. Our previous work showed that Nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing protein 5 (NLRC5) is involved in bone destruction associated with periodontitis, but its potential and mechanism in regulating bone tissue repair and regeneration have not been fully elucidated. A monocortical bone defect model was established in the mouse femur to assess the impact of NLRC5 on in situ bone healing and regeneration. Mouse bone marrow-derived mesenchymal stem cells (BMSCs) were isolated to evaluate the effects of NLRC5 on osteogenic differentiation, proliferation, and migration. RNA sequencing was used to explore the direct regulatory mechanism of NLRC5 on osteogenic differentiation of mouse BMSCs. Mass cytometry was employed to examine the effect of NLRC5 on the bone marrow immune microenvironment, followed by in vitro validation experiments. Loss of NLRC5 impaired the healing and regeneration of femoral bone defects in mice, and led to a high inflammatory state in the early stage of healing. The absence of NLRC5 inhibited the osteogenic differentiation ability of BMSCs, and could be restored by NLRC5 overexpression, which was achieved through activation of the phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway. Mass cytometry data revealed that NLRC5 may serve as an important factor in maintaining the differentiation and maturation of regulatory T cells (Tregs). By modulating the levels of inflammatory cytokines, NLRC5 further influences the osteogenic differentiation of BMSCs. NLRC5 serves as a key regulator and promising candidate for bone repair. NLRC5 contributes to bone regeneration through a dual mechanism: it promotes BMSCs osteogenic differentiation, at least in part via the PI3K/AKT/β-catenin signaling pathway, and indirectly modulates the local immune microenvironment to facilitate bone repair.

Indexed as

Bone RegenerationCell DifferentiationCellular MicroenvironmentIntracellular Signaling Peptides and ProteinsMesenchymal Stem CellsOsteogenesisAnimalsBone Marrow CellsCell ProliferationMaleMiceMice, Inbred C57BLProto-Oncogene Proteins c-aktSignal TransductionIntracellular Signaling Peptides and ProteinsNLRC5 protein, mouseProto-Oncogene Proteins c-aktBMSCsbone healingimmune microenvironmentNLRC5osteogenic differentiation

Identifiers

PMID42511833

DOI10.3390/ijms27146489

PMCPMC13411262

What OpenQuestion holds

Textmetadata

LicenceCC BY

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.