Reuterin drives osteogenic and suppresses adipogenic differentiation of bone marrow mesenchymal stem cells via BMP/SMAD signaling to ameliorate osteoporosis.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Osteoporosis, a prevalent skeletal condition defined by diminished bone density and disrupted microarchitecture, dramatically elevates fracture risk. Its pathophysiology is now understood to extend beyond classic remodeling imbalances to include a pivotal shift in bone marrow mesenchymal stem cell (BMSC) differentiation, where adipogenesis is favored over osteogenesis-a key feature of aging and estrogen deficiency. The emerging "gut-bone axis" suggests that microbiota-derived metabolites can systemically influence skeletal homeostasis, presenting new therapeutic possibilities. This research uncovers the direct osteoanabolic and anti-adipogenic properties of Reuterin (3-hydroxypropionaldehyde, Reut), a principal antimicrobial metabolite from Lactobacillus reuteri. In vitro, Reut (5-20 μM) showed excellent cytocompatibility, dose-dependently boosting osteogenic differentiation (increased ALP activity and mineralization) while effectively suppressing adipogenic differentiation (decreased lipid accumulation) in BMSCs. Mechanistically, Reut specifically activated the canonical BMP-Smad pathway, demonstrated by the rapid phosphorylation and nuclear translocation of Smad1/5/9 and the upregulated expression of its direct targets (ID1, ID2). This activation was crucial, as the BMP receptor inhibitor LDN-193189 completely negated Reut's effects. In an ovariectomized (OVX) rat model, syst

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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