Background <p>Osteoblast formation and function are essential for regulating bone disorders such as osteoporosis. Recent studies have confirmed that long non-coding RNAs (lncRNAs) from exosomes (ExOs) are involved in osteoblast proliferation and differentiation. This study investigated the role of bone marrow mesenchymal stem cell (BMSC)-derived exosomal lncRNA-ZFAS1 in regulating osteoblasts.</p> Methods <p>Human BMSCs and derived exosomes (BMSC-EXOs) were isolated and characterized. ZFAS1, miR-9, and IGF-1 levels in BMSC-EXOs and osteoblasts were measured by RT-qPCR and Western blot. ZFAS1 localization was determined by fluorescence in situ hybridization (FISH) and nuclear-cytoplasmic fractionation. ZFAS1 interactions with miR-9 and IGF-1 were confirmed via dual-luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP). The effects of the ZFAS1/miR-9 axis on osteoblast proliferation and differentiation were examined using CCK-8, Alizarin Red staining, and ALP staining assays.</p> Results <p>BMSC-EXOs exhibited elevated ZFAS1 levels and efficiently delivered this lncRNA to osteoblasts. Through this mechanism, ZFAS1 enhanced osteoblast proliferation and differentiation. Mechanistically, ZFAS1 inhibited miR-9 expression, and downregulation of miR-9 reversed the suppression of osteoblast proliferation and differentiation induced by ZFAS1 silencing. The decrease in miR-9 leads to an increase in IGF-1, thereby promoting the proliferation and differentiation of osteoblasts.</p> Conclusions <p>We have shown that ZFAS1 from BMSC-derived EXOs enhances the proliferation and differentiation of osteoblasts by regulating the miR-9/IGF-1 signaling axis. This discovery provides novel insights into mechanisms of osteoblast proliferation and differentiation, and identifies potential therapeutic targets for treating associated diseases.</p>