# Diacerein Downregulates Nfkb, Induces ALP Activity and Inhibits Osteoblast Apoptosis in Alveolar Bone of Rats with Periodontitis

**Authors:** Paulo Sérgio Cerri, Lucas de Andrade Rodrigues, Lays Cristina Gouvea, Gabriella de Oliveira, Estela Sasso-Cerri

PMC · DOI: 10.3390/biomedicines14020306 · Biomedicines · 2026-01-29

## TL;DR

Diacerein reduces inflammation and prevents bone cell death in rats with periodontitis, helping protect alveolar bone.

## Contribution

This study shows diacerein's novel role in downregulating Nfkb and inhibiting osteoblast apoptosis in periodontitis.

## Key findings

- Diacerein reduced TNF-α and IL-1β immunoexpression while increasing ALP activity and bone area.
- Diacerein decreased Nfkb1 expression and increased Bmp2 and IL-10 in periodontitis-affected rats.
- Diacerein significantly reduced osteoblast apoptosis compared to the control group.

## Abstract

Objectives: We evaluated the effect of diacerein, an anti-inflammatory drug, on the activity and survival of alveolar bone osteoblasts in rats with periodontitis. Methods: The rats with periodontitis received diacerein (PDG) or saline solution (PSG) for 7, 15 and 30 days. In gingiva samples, Nfkb1 and Bmp2 gene expressions were evaluated, and maxillae were processed for light and transmission electron microscopy. Results: In PDG, the tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) immunoexpression decreased in parallel with the increase in alkaline phosphatase (ALP) and bone area over time. At 15 and 30 days, Nfkb1 expression decreased in PDG compared to PSG, whereas at 30 days, the Bmp2 expression was greater in PDG than in PSG. Immunofluorescence for IL-10, an anti-inflammatory cytokine, was greater in PDG than in PSG at 15 and 30 days. In PSG, the significant increase in the number of TUNEL-positive osteoblasts was accompanied by the presence of osteoblasts with condensed chromatin nuclei or caspase-3-immunolabelled osteoblasts. In contrast, the number of TUNEL-positive osteoblasts was significantly lower in PDG than in PSG specimens at all time points. Conclusions: Therefore, the diacerein-induced TNF-α and IL-1β inhibitory effect caused Nfkb1 downregulation and, hence, prevented apoptosis in osteoblasts. The increased ALP activity and IL-10 in PDG indicate that diacerein mitigates periodontitis impact on alveolar bone in rat molars.

## Linked entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], BMP2 (bone morphogenetic protein 2) [NCBI Gene 650]
- **Proteins:** TNF (tumor necrosis factor), IL1B (interleukin 1 beta), IL10 (interleukin 10), ALPP (alkaline phosphatase, placental), Casp3 (caspase 3)
- **Chemicals:** diacerein (PubChem CID 26248)
- **Diseases:** periodontitis (MONDO:0005076)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, Bmp2 (bone morphogenetic protein 2) [NCBI Gene 12156] {aka Bmp2a}, SP7 (Sp7 transcription factor) [NCBI Gene 121340] {aka OI11, OI12, OSX, osterix}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}, alp (alopecia, recessive) [NCBI Gene 11691], BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, Dntt (DNA nucleotidylexotransferase) [NCBI Gene 294051], RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860] {aka AML3, CBF-alpha-1, CBFA1, CCD, CCD1, CLCD}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Spp1 (secreted phosphoprotein 1) [NCBI Gene 20750] {aka 2AR, Apl-1, BNSP, BSPI, Bsp, ETA-1}, Psgb1 (pregnancy-specific beta 1-glycoprotein) [NCBI Gene 59313] {aka Psg}, Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Sp7 (Sp7 transcription factor) [NCBI Gene 300260] {aka Osx}, Bglap2 (bone gamma-carboxyglutamate protein 2) [NCBI Gene 12097] {aka BGP2, Bglap1, Bgp, Og2, mOC-B}, Runx2 (RUNX family transcription factor 2) [NCBI Gene 367218] {aka CBF-alpha-1, Cbfa1, OSF-2}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Sparc (secreted acidic cysteine rich glycoprotein) [NCBI Gene 20692] {aka BM-40, ON}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Bmp2 (bone morphogenetic protein 2) [NCBI Gene 29373], Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, MMP8 (matrix metallopeptidase 8) [NCBI Gene 4317] {aka CLG1, HNC, MMP-8, PMNL-CL}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, Pdlim3 (PDZ and LIM domain 3) [NCBI Gene 114108] {aka Actn2lp, Alp}, Runx2 (runt related transcription factor 2) [NCBI Gene 12393] {aka AML3, CBF-alpha-1, Cbf, Cbfa-1, Cbfa1, LS3}, Nfkb1 (nuclear factor kappa B subunit 1) [NCBI Gene 81736] {aka EBP-1, NF-kB, NFKB-p50, p50}, Casp1 (caspase 1) [NCBI Gene 25166] {aka Ice, Il1bc, p45}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Actb (actin, beta) [NCBI Gene 81822] {aka Actx}, Tnfsf11 (TNF superfamily member 11) [NCBI Gene 117516] {aka ODF, OPGL, RANKL, TRANCE}, Sp7 (Sp7 transcription factor 7) [NCBI Gene 170574] {aka 6430578P22Rik, C22, Osx}
- **Diseases:** resorption (MESH:D014091), bacterial infection (MESH:D001424), inflammatory drug (MESH:D000081015), CG (MESH:C536209), OA (MESH:D010003), periodontal disease (MESH:D010510), overdose (MESH:D062787), immunoinflammatory disease (MESH:D004194), injury to (MESH:D014947), arthritis (MESH:D001168), inflammatory (MESH:D007249), Periodontitis (MESH:D010518), tooth loss (MESH:D016388), rheumatoid arthritis (MESH:D001172), pain (MESH:D010146), bone loss (MESH:D001847), Alveolar Bone Loss (MESH:D016301), edema (MESH:D004487)
- **Chemicals:** propylene oxide (MESH:C009068), water (MESH:D014867), methylene blue (MESH:D008751), ketamine hydrochloride (MESH:D007649), lipopolysaccharide (MESH:D008070), pyrophosphate (MESH:C107241), paraformaldehyde (MESH:C003043), glutaraldehyde (MESH:D005976), 3,3'-diaminobenzidine (MESH:D015100), rhein (MESH:C020491), DAB (MESH:C000469), methylene (MESH:C030011), formaldehyde (MESH:D005557), ethanol (MESH:D000431), Toluidine blue (MESH:D014048), nitric oxide (MESH:D009569), DAPI (MESH:C007293), calcium (MESH:D002118), alizarin red (MESH:C010078), hydrogen peroxide (MESH:D006861), S2345 (-), paraffin (MESH:D010232), PDG (MESH:C022270), Artrodar (MESH:C025292), sodium citrate (MESH:D000077559), inorganic phosphate (MESH:D010710), Pi (MESH:D010716), osmium tetroxide (MESH:D009993), haematoxylin (MESH:D006416), sodium phosphate (MESH:C018279), xylene (MESH:D014992), dUTP (MESH:C027078), xylazine hydrochloride (MESH:D014991), EDTA (MESH:D004492), Araldite (MESH:C005752), uranyl acetate (MESH:C005460), hydroxyapatite (MESH:D017886), Alexa Fluor 488 (MESH:C000711379)
- **Species:** Porphyromonas gingivalis (species) [taxon 837], Treponema denticola (species) [taxon 158], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Tannerella forsythia (species) [taxon 28112]

## Full text

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## Figures

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## References

62 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938624/full.md

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Source: https://tomesphere.com/paper/PMC12938624