Dermatan sulfate regulates apoptosis and osteogenic differentiation of hBMSCs through estrogen-like effects.

Although dermatan sulfate (DS) has been known to have an impact on bone development, its effects on the apoptosis and osteogenic differentiation of human bone marrow mesenchymal stromal cells (hBMSCs) are still poorly understood. The present study investigated these effects and the underlying mechanism. Transcriptomic analysis revealed that DS significantly altered gene expression patterns associated with apoptosis and osteogenesis. Functionally, DS promoted hBMSC proliferation, reduced apoptosis, and potently enhanced osteogenic differentiation and mineralization. Crucially, knockdown of ESR1 attenuated these pro-osteogenic and anti-apoptotic effects of DS. Molecular docking analysis further indicated that DS binds to estrogen receptor α (ERα) with affinity comparable to estradiol. Collectively, our results demonstrate that DS exerts estrogen-like effects, primarily mediated through ERα, to promote hBMSC survival and osteogenic differentiation. This novel mechanism highlights the therapeutic promise of DS for enhancing bone formation in estrogen-deficient conditions, such as postmenopausal osteoporosis (PMOP).