GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE229nnn/GSE229371/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE229371GEOGSEfalseReduced expression of Semaphorin3A derived from osteoclasts cause lymphatic expansion in GSD mouse modelGorham-Stout disease (GSD) is a sporadic chronic disease characterized by progressive bone dissolution, absorption, disappearance, and lymphatic vessel infiltration in bone marrow cavities. Although the osteolytic mechanism of GSD has been widely studied, the cause of lymphatic hyperplasia of GSD is rarely touched. In this study, Through comparing RNA expression profile in Osteoclast (OC) with Osteoclast precursors (OCP) by RNA sequencing, we identified a new factor, Semaphorin 3A (Sema3A), as an osteoprotective factor, which is involved in the lymphatic expansion of GSD. Compared to OCP, OC enhanced the growth, migration, and tube formation of lymphatic endothelial cells (LECs), in which the expression of Sema3A is low compared to OCP. In the presence of recombinant Sema3A, the growth, migration, and tube formation of LECs were inhibited, further comfirmed the effect of Sema3A on LECs. Using LEC-induced GSD mouse model, the effect of Sema3A was examined by injecting lentiviral expressing Sema3A into the tibiae. We found that the overexpression of Sema3A in tibiea suppressed the expansion of LECs and alleviated the bone loss, whereas the injection with lentiviral expressing Sema3A shRNA into the tibiae caused GSD-like phenotypes. Histological staining further demonstratsed the Osteoclasts decreased and osteocalcin were increased after the Seme3A treatment with lentiviral of Sema3A compared with the control. Combined with the role of Seme3A on osteoprotection, we propose that reduced Sema3A in OCs is one of pathogenesis of GSD and expressing Sema3A represents a new approach for treatment of GSD.2026/04/01GSE229371GSM7159373GSM7159368GSM7159369GSM7159371GSM7159372GSM715937028330229371Mus musculus