Evidence mapPaperPMID 39968082Full record

ArticleIranian journal of basic medical sciences2025

Targeting dipeptidyl peptidase-8/9 to combat inflammation-induced osteoclastogenesis in RAW264.7 macrophages and analysis of anti-osteoclastogenesis potential of chrysin.

Syed Sufian Ahmad, Faraha Ahmed, Sayeed Ahmad, Anuja Krishnan, Mohammad Ahmed Khan

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Article in Iranian journal of basic medical sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
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

Who cites it

2 citing papers in PubMed.

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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.

Syed Sufian AhmadDepartment of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, Hamdard, New Delhi - 110062, India.
Faraha AhmedDepartment of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, Hamdard, New Delhi - 110062, India.
Sayeed AhmadBioactive Natural Product Laboratory, School of Pharmaceutical Education and Research, Jamia Hamdard, Hamdard, New Delhi - 110062, India.
Anuja KrishnanDepartment of Molecular Medicine, School of Interdisciplinary Science and Technology, Jamia Hamdard, Hamdard, New Delhi - 110062, India.
Mohammad Ahmed KhanDepartment of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, Hamdard, New Delhi - 110062, India.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objectives: Osteoclasts drive bone resorption under inflammation, with cytokines promoting osteoclastogenesis. The role of proline enzymes like dipeptidyl peptidase-8 and 9 (DPP-8/9) in this process remains unclear. This study aimed to explore the DPP-8/9 involvement in inflammation-driven osteoclastogenesis using the RAW264.7 macrophage model. Materials and Methods: Receptor activator of nuclear factor-κB ligand (RANKL) and lipopolysaccharide (LPS) induced osteoclastogenesis, raising interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and IL-23 levels. Using RAW264.7 cells, DPP-8/9 protein and tartrate-resistant acid phosphatase (TRAPc) were assayed. Antibodies for cluster of differentiation (CD86 and CD206) were used to analyze macrophage polarization, while molecular docking was used to assess flavonoid binding to DPP-8/9. Western blot confirmed DPP-8/9 expression in treated macrophages. Results: Administering RANKL and LPS increased IL-6 and TNF-α levels, significantly promoting osteoclastogenesis in RAW264.7 macrophages. This treatment also elevated the levels of the inflammatory macrophage marker IL-23. Osteoclast formation was confirmed by measuring TRAPc levels in the culture. Analysis of the cell supernatant revealed elevated DPP-8/9 levels in the RANKL+LPS group. Inhibition of DPP-8/9 with 1G244 decreased inflammatory cytokines and TRAPc levels in the cell culture. Molecular docking analysis of various flavonoids identified chrysin as a potential molecule with sufficient binding energy against DPP-8/9, a finding confirmed by blotting assay. Conclusion: This study emphasizes the involvement of DPP-8/9 in inflammatory osteoclastogenesis in RAW264.7 macrophages. Inhibition of DPP-8/9 reduced osteoclastogenesis markers and inflammatory cytokines levels, indicating decreased osteoclast formation. Additionally, chrysin demonstrated potential as an anti-DPP-8/9 agent, highlighting its possible role in future therapeutic strategies targeting inflammation-induced osteoclastogenesis.

Indexed as

ChrysinDipeptidyl peptidase 8Dipeptidyl peptidase 9Inflammatory – osteoclastogenesisM1 macrophageRAW264.7 cells

Identifiers

PMID39968082
PMCPMC11831742

What Socratic holds

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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.