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A Letter Matters: ADRB2 rs1042713 c.46A Modulates Anti-osteogenic Effect of Epinephrine in Human Mesenchymal Stem Cells.

Olga Krasnova·Julia Sopova·Valeriia Borodii·Polina Semenova·Olga Bystrova·Irina Neganova
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Abstract

Osteoporosis (OP) is a systemic bone disease affecting millions worldwide, characterized by long-term asymptomatic development that manifests in low-energy fractures. Due to their high stability, genetic markers represent a promising strategy for early diagnostics. The ADRB2 rs1042713 polymorphism is one such marker, considered as a potential predictor for OP. Although the anti-osteogenic role of the β2-adrenergic receptor is well-established, debate continues on which allele (G or A) of this polymorphism drives bone deterioration. In this study, we examined the influence of the ADRB2 rs1042713 G/G and A/A variants on osteogenic differentiation in patient-derived mesenchymal stem cells (MSCs) under treatment with the endogenous agonist epinephrine. We show that epinephrine (whose levels are often elevated in comorbid conditions) drastically impairs osteogenic differentiation, specifically at the matrix mineralization stage in MSCs A/A. Epinephrine fails to activate the canonical β2-adrenergic receptor pathway and promotes receptor perinuclear and nuclear localization in MSCs A/A. Crucially, metformin, a common anti-diabetic drug, rescues this anti-osteogenic effect. These results open new perspectives for early diagnostics by identifying epinephrine sensitivity as a critical factor, while also suggesting a potential therapeutic strategy to counteract epinephrine detrimental effect in individuals carrying the ADRB2 rs1042713 A-allele.

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HumansMesenchymal Stem CellsEpinephrineReceptors, Adrenergic, beta-2Cell DifferentiationOsteogenesisPolymorphism, Single NucleotideAllelesMesenchymal stem cellsOsteoporosisSingle nucleotide polymorphism.β2-adrenergic receptorJournal Article

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Olga Krasnova, Julia Sopova, Valeriia Borodii, Polina Semenova, Olga Bystrova, Irina Neganova. 2026-07-01. A Letter Matters: ADRB2 rs1042713 c.46A Modulates Anti-osteogenic Effect of Epinephrine in Human Mesenchymal Stem Cells.. https://doi.org/10.1007/s12015-026-11185-7

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Journal Article resourceAlleles subjectHumans subjectJournal Article subjectPolymorphism, Single Nucleotide subject

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