Tier 4 — mechanistic

Alpha ketoglutarate exerts a pro-osteogenic effect in osteoblast cell lines through activation of JNK and mTOR/S6K1/S6 signaling pathways

Żurek A, Mizerska-Kowalska M, Sławińska-Brych A, Kaławaj K, Bojarska-Junak A, Kandefer-Szerszeń M, Zdzisińska B
Toxicology and Applied Pharmacology 2019 374:53-64

Bibliography

PubMed
PMID 31051157
DOI
10.1016/j.taap.2019.04.024
Funding
Academic funding details are reported in the full article.
Competing interests
No commercial Ca-AKG human intervention was tested.

Study snapshot

DesignIn-vitro osteoblast differentiation study.
ModelHuman hFOB 1.19 and mouse MC3T3-E1 osteoblast cell lines.
SampleCell-culture study with repeated experimental assays.
InterventionDisodium alpha-ketoglutarate exposure in osteoblast cultures.
DurationStudy-specific differentiation protocols.
EndpointsRUNX2 and Osterix; Osteoblast differentiation markers; Mineralization; JNK signaling; mTOR/S6K1/S6 signaling; GPR99

What the study showed, in plain terms

This study addresses the bone-forming side of AKG biology by testing osteoblasts directly.

AKG increased osteoblast differentiation markers and mineralization through JNK and mTOR/S6K1/S6 signaling without increasing cell proliferation.

It is useful mechanistic support for the bone-health corpus, but it is a cell-line experiment and does not demonstrate improved human bone density or fracture outcomes.

Key findings

  • AKG increased osteoblast differentiation and mineralization markers.
  • JNK and mTOR/S6K1/S6 signaling were required for the effect.
  • The AKG salt effect appeared independent of GPR99 activation.

What this study can and cannot tell us

  • In-vitro study only.
  • Disodium AKG is not calcium AKG.
  • No systemic pharmacology or clinical bone outcome.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology