Evidence mapPaperPMID 40807354Full record

ReviewMolecules (Basel, Switzerland)2025

Docosahexaenoic Acid Inhibits Osteoclastogenesis via FFAR4-Mediated Regulation of Inflammatory Cytokines.

Jinghan Ma, Hideki Kitaura, Fumitoshi Ohori, Aseel Marahleh, Ziqiu Fan, Angyi Lin, Kohei Narita, Kou Murakami, Hiroyasu Kanetaka

Abstract readReview
In one paragraph

Review in Molecules (Basel, Switzerland), 2025. 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

9 authors.

Jinghan MaDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.
Hideki KitauraDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.ORCID 0000-0003-3249-4247
Fumitoshi OhoriDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.
Aseel MarahlehFrontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai 980-8575, Miyagi, Japan.
Ziqiu FanDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.ORCID 0009-0009-8940-4979
Angyi LinDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.ORCID 0009-0001-8053-0858
Kohei NaritaDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.
Kou MurakamiDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.
Hiroyasu KanetakaDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.

Funding

Japan Society for the Promotion of Science 24K23573Japan Society for the Promotion of Science 25K02830
6 · The paper itself

Abstract

Osteoclastogenesis-the activation and differentiation of osteoclasts-is one of the pivotal processes of bone remodeling and is regulated by RANKL/RANK signaling, the decoy function of osteoprotegerin (OPG), and a cascade of pro- and anti-inflammatory cytokines. The disruption of this balance leads to pathological bone loss in diseases such as osteoporosis and rheumatoid arthritis. FFAR4 (Free Fatty Acid Receptor 4), a G protein-coupled receptor for long-chain omega-3 fatty acids, has been confirmed as a key mediator of metabolic and anti-inflammatory effects. This review focuses on how FFAR4 acts as the selective receptor for the omega-3 fatty acid docosahexaenoic acid (DHA). It activates two divergent signaling pathways. The Gαq-dependent cascade facilitates intracellular calcium mobilization and ERK1/2 activation. Meanwhile, β-arrestin-2 recruitment inhibits NF-κB. These collective actions reshape the cytokine environment. In macrophages, DHA-FFAR4 signaling lowers the levels of TNF-α, interleukin-6 (IL-6), and IL-1β while increasing IL-10 secretion. Consequently, the activation of NFATc1 and NF-κB p65 is profoundly suppressed under TNF-α or RANKL stimulation. Additionally, DHA modulates the RANKL/OPG axis in osteoblastic cells by suppressing RANKL expression, thereby reducing osteoclast differentiation in an inflammatory mouse model.

Indexed as

CytokinesDocosahexaenoic AcidsOsteoclastsOsteogenesisReceptors, G-Protein-CoupledAnimalsCell DifferentiationHumansRANK LigandSignal TransductionCytokinesDocosahexaenoic AcidsFFAR4 protein, humanRANK LigandReceptors, G-Protein-Coupledbone metabolismdocosahexaenoic acidFFAR4osteoclast

Identifiers

PMID40807354
PMCPMC12348860

What Socratic 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 Socratic graph.