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LL-37 regulates odontogenic differentiation of dental pulp stem cells in an inflammatory microenvironment.
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- Author(s): Ma Y;Ma Y; Liu X; Liu X; Dai R; Dai R; Li Q; Li Q; Cao CY; Cao CY
- Source:
Stem cell research & therapy [Stem Cell Res Ther] 2024 Dec 18; Vol. 15 (1), pp. 469. Date of Electronic Publication: 2024 Dec 18.- Publication Type:
Journal Article- Language:
English - Source:
- Additional Information
- Source: Publisher: BioMed Central Country of Publication: England NLM ID: 101527581 Publication Model: Electronic Cited Medium: Internet ISSN: 1757-6512 (Electronic) Linking ISSN: 17576512 NLM ISO Abbreviation: Stem Cell Res Ther Subsets: MEDLINE
- Publication Information: Original Publication: London : BioMed Central
- Subject Terms: Dental Pulp*/cytology ; Dental Pulp*/metabolism ; Cathelicidins* ; Cell Differentiation*/drug effects ; Odontogenesis*/drug effects ; Stem Cells*/metabolism ; Stem Cells*/cytology ; Stem Cells*/drug effects ; Cell Proliferation*/drug effects; Humans ; Antimicrobial Cationic Peptides/pharmacology ; Antimicrobial Cationic Peptides/metabolism ; Cell Movement/drug effects ; Inflammation/metabolism ; Inflammation/pathology ; Cellular Microenvironment/drug effects ; Extracellular Matrix Proteins/metabolism ; Extracellular Matrix Proteins/genetics ; Cells, Cultured ; Adolescent ; Young Adult ; Tumor Necrosis Factor-alpha/metabolism ; Phosphoproteins ; Sialoglycoproteins
- Abstract: Background: Inflammation often causes irreversible damage to dental pulp tissue. Dental pulp stem cells (DPSCs), which have multidirectional differentiation ability, play critical roles in the repair and regeneration of pulp tissue. However, the presence of proinflammatory factors can affect DPSCs proliferation, differentiation, migration, and other functions. LL-37 is a natural cationic polypeptide that inhibits lipopolysaccharide (LPS) activity, enhances cytokine production, and promotes the migration of stem cells. However, the potential of LL-37 in regenerative endodontics remains unknown. This study aimed to investigate the regulatory role of LL-37 in promoting the migration and odontogenic differentiation of DPSCs within an inflammatory microenvironment. These findings establish an experimental foundation for the regenerative treatment of pulpitis and provide a scientific basis for its clinical application.
Materials and Methods: DPSCs were isolated via enzyme digestion combined with the tissue block adhesion method and identified via flow cytometry. The impact of LL-37 on the proliferation of DPSCs was evaluated via a CCK-8 assay. The recruitment of DPSCs was assessed through a transwell assay. The mRNA expression levels of inflammatory and aging-related genes were assessed via reverse transcription‒polymerase chain reaction (RT‒PCR), western blotting, and enzyme‒linked immunosorbent assay (ELISA). The odontogenic differentiation of DPSCs was assessed through alkaline phosphatase (ALP) staining, alizarin red staining, and RT‒PCR analysis.
Results: LL-37 has the potential to enhance the migration of DPSCs. In an inflammatory microenvironment, LL-37 can suppress the expression of genes associated with inflammation and aging, such as TNF-α, IL-1β, IL-6, P21, P38 and P53. Moreover, it promotes odontogenic differentiation in DPSCs by increasing ALP activity, increasing calcium nodule formation, and increasing the expression of dentin-related genes such as DMP1, DSPP and BSP.
Conclusion: These findings suggest that the polypeptide LL-37 facilitates the migration of DPSCs and plays a crucial role in resolving inflammation and promoting cell differentiation within an inflammatory microenvironment. Consequently, LL-37 has promising potential as an innovative therapeutic approach for managing inflammatory dental pulp conditions.
Competing Interests: Declarations. Ethical approval and consent to participate: The extraction procedures of human DPSCs were conducted in accordance with the Declaration of Helsinki, and informed consent was obtained from the donors and/or their guardians before the tooth collection. The extraction procedures of human DPSCs in this study were approved by the Ethics Committee of Anhui Medical University. (Project title: The key physicochemical factors and mechanisms of collagen intra/extra-fibrillar mineralization mediated by polyelectrolyte-calcium phosphate prenucleation clusters; Approval No: LLSC20240974; Date of approval: 2024–03-01). Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.
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- Contributed Indexing: Keywords: Dental pulp stem cells; Lipopolysaccharide; Odontogenic differentiation; Polypeptide; Pulpitis
- Accession Number: 0 (Cathelicidins)
0 (Antimicrobial Cationic Peptides)
0 (Extracellular Matrix Proteins)
0 (DMP1 protein, human)
0 (dentin sialophosphoprotein)
0 (Tumor Necrosis Factor-alpha)
0 (Phosphoproteins)
0 (Sialoglycoproteins) - Publication Date: Date Created: 20241219 Date Completed: 20241219 Latest Revision: 20241219
- Publication Date: 20241219
- Accession Number: 10.1186/s13287-024-04075-7
- Accession Number: 39696668
- Source:
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