Igsf10 Alleviate Metabolic Bone Disorders By Enhancing Osteogenic Bone Formation

To investigate the systemic role of IGSF10 in regulating bone homeostasis and remodeling, focusing on its molecular interplay with osteogenic networks. Osteoblast-specific IGSF10-knockout mice (Oc-Cre;Igsf10flox/flox, 8-week-old females) and Igsf10flox controls were analyzed. Bone microarchitecture was assessed by micro-CT. Osteoclast activity was evaluated via TRAP staining. Bone marrow stromal cells (BMSCs) from knockout and control mice were subjected to osteogenic induction in vitro, with or without IGSF10 treatment. Primary human PDLCs were cultured in basal medium or osteogenic induction medium (OIM) ± recombinant IGSF10. Osteogenic markers (Runx2, ALP, Bsp) were analyzed by qPCR and Western blot. Mineralization was assessed via ALP staining (day 7) and Alizarin Red S quantification (day 14). RNA-seq and pathway enrichment analysis were performed on IGSF10-treated PDLCs to identify regulatory networks. Statistical analysis was performed using unpaired t-test and one-way ANOVA. Osteoblast-specific IGSF10 knockout mice demonstrated reduced trabecular bone density and thickness in femurs and mandibles under basal conditions, independent of osteoclast activity. BMSCs from knockout mice exhibited impaired osteogenic differentiation (reduced Runx2, ALP, and mineralization), which was partially restored by exogenous IGSF10, while IGSF10 synergized with osteogenic signals to enhance mineralization in human periodontal fibroblasts. RNA-seq revealed that IGSF10 activated interferon-associated transcriptional networks during osteogenic programming, suggesting a novel regulatory axis in bone formation. IGSF10 regulates bone formation by enhancing differentiation and mineralization through activation of interferon-associated transcriptional networks, providing a potential therapeutic target for bone regeneration.