Tier 4 — mechanistic

Elevation of Intracellular Alpha-Ketoglutarate Levels Inhibits Osteoclastogenesis by Suppressing the NF-κB Signaling Pathway in a PHD1-Dependent Manner

Tian J, Bao X, Yang F, Tang X, Jiang Q, Li Y, Yao K, Yin Y

Nutrients 2023 15(3):701

Bibliography

PubMed: PMID 36771407
PubMed Central: PMC9921543
DOI: 10.3390/nu15030701
Funding: National Natural Science Foundation of China and Chinese Academy of Sciences programs supported the study.
Competing interests: The paper reports no Ca-AKG retail-product clinical trial.

Design	Mechanistic in-vitro osteoclast differentiation study.
Model	Primary bone-marrow-derived macrophages and RAW264.7 cells.
Sample	Cell-culture experiments with multiple biological replicates.
Intervention	Dimethyl-AKG used to elevate intracellular AKG during RANKL-induced osteoclastogenesis.
Duration	Three- to five-day differentiation experiments.
Endpoints	Osteoclast differentiation; NF-κB signaling; Oxidative phosphorylation; PHD1 dependency; TRAP activity

This paper examines the bone-resorbing side of AKG biology.

Raising intracellular AKG with cell-permeable dimethyl-AKG suppressed osteoclast differentiation and NF-κB signaling in a PHD1-dependent manner.

Because the intervention was dimethyl-AKG in cells, this paper should not be used as evidence that oral Ca-AKG prevents osteoporosis.

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Last verified 20 September 2026