Hepatic selenoprotein P impairs bone formation via osteoblastic IGF-1 resistance
Authors' conclusion
Together, these findings identify hepatic selenoprotein P as a negative regulator of bone formation and define a hepato-osteogenic reductive stress axis that links metabolic stress to impaired skeletal integrity.
Study context
- Population
- Mice on high-fat, high-sucrose diet; calvaria-derived osteoblast cultures; a general population cohort
- Comparison
- Selenop deficiency vs intact Selenop; selenoprotein P exposure vs none in osteoblast cultures
- Outcome
- Hepatic selenoprotein P and bone formation
Methodological detailsmouse genetic models, high-fat, high-sucrose diet, osteoblast cell culture, cross-sectional cohort analysis
- Mouse genetic models
- High-fat, high-sucrose diet
- Osteoblast cell culture
- Cross-sectional cohort analysis
Main finding
As reported in the abstract
- Whole-body Selenop deficiency preserved trabecular bone mass, bone formation, bone stiffness and cortical bone defect repair
- Hepatocyte-specific Selenop deficiency also preserved trabecular bone mass
- Histomorphometry: selenoprotein P suppressed osteoblast activation, osteoclast indices not materially altered
- In osteoblast cultures, selenoprotein P inhibited IGF-1-induced phosphorylation of IGF-1 receptor, IRS-1, PI3K, PDK1 and Akt, reduced alkaline phosphatase activity, matrix mineralization and osteogenic gene expression, and blunted receptor-proximal ROS generation
- LRP1 was the predominant candidate receptor during osteogenic differentiation
- Osx-Cre/+ Lrp1fl/fl cultures: reduced cell-associated human selenoprotein P; inhibitory effects on IGF-1 signaling and osteoblast maturation absent
- In vivo IGF-1 receptor blockade eliminated the skeletal protection of Selenop deficiency
Further findings
Serum selenoprotein P and OSI, general population cohort
- Serum selenoprotein P not significantly associated with OSI across the full cohort
- Highest quintile: inverse association between high circulating selenoprotein P and bone mass
- Cross-sectional analysis
- Exploratory analyses
Original publication
Hepatic selenoprotein P impairs bone formation via osteoblastic IGF-1 resistance. J Bone Miner Res. Published 25 September 2026. doi:10.
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