Early BMP7 Exposure Enhances Brown Adipogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells

Brown adipose tissue (BAT) dissipates energy via non-shivering thermogenesis, making it a promising therapeutic target for metabolic diseases. However, effective strategies for directing human stem cells toward brown adipocyte lineage remain to be fully established. Here, as an early commitment modulation study, we investigated whether stage-specific exposure to bone morphogenetic protein 7 (BMP7) during initial induction enhances brown adipocyte-like features and β-adrenergic responsiveness in tonsil-derived mesenchymal stem cells (TMSCs).

TMSCs were induced to differentiate into white adipocyte-like cells (WA) or brown adipocyte-like cells using a two-step protocol. Among the brown adipogenic groups, BMP7 (50 ng/mL) was additionally administered during the early commitment stage (step 1) in one group (BA + BMP7) but not the other (BA), while both groups received BMP7 throughout the subsequent step 2 induction, allowing the stage-specific effect of early BMP7 priming to be evaluated. Lineage commitment and brown adipocyte-like features were assessed via Oil Red O staining, qPCR, western blotting, MitoTracker staining, and cAMP responsiveness upon β-adrenergic stimulation (isoproterenol).

Early BMP7 priming during the initial commitment stage effectively promoted brown adipocyte lineage commitment. Compared with the WA and BA group, BA+BMP7 cells exhibited significantly increased UCP1 protein expression, along with non-significant upward trends in ZIC1 and PGC1α, and a significant increase in the progenitor commitment marker Myf5. Furthermore, brown adipogenic differentiation significantly increased mitochondrial mass, showing an additional upward trend in the early BMP7-primed group, whereas β-adrenergic functional responsiveness distinguished the two brown adipogenic groups: upon isoproterenol stimulation, BA + BMP7 cells exhibited an increase in intracellular cAMP accumulation relative to their own basal state, alongside enhanced HSL phosphorylation, a pattern not observed to the same extent in brown-differentiated cells without early BMP7 priming.

This early commitment modulation study demonstrates that temporal BMP7 exposure enhances brown adipocyte-like features and adrenergic sensitivity in TMSCs. Early stage-specific signaling modulation provides a viable strategy for directing stem cell lineage commitment toward brown adipocyte-like phenotypes for metabolic research.