Osteosarcoma (OS) is a bone malignancy affecting children and adolescents. Retinoblastoma (RB) patients with germline RB1 mutations are susceptible to osteosarcoma in the second decade of their life. Several studies, particularly in mice, have revealed a role for RB1 in osteogenesis. Since, there is species specific difference attributed in retinoblastoma tumorigenesis between mice and human, we assumed, it is worthwhile exploring the role of RB1 in osteogenesis and thus onset of osteosarcoma. In this study, we analyzed the temporal gene expression of the osteogenic markers, tumor suppressor genes and hormone receptors associated with growth spurt during in vitro osteogenesis of mesenchymal stem cells derived from orbital adipose tissue of germline RB patients and compared it with those with wild type RB1 gene. Mesenchymal stem cells with the heterozygous RB1 mutation showed reduced expression of RB1 and other tumor suppressor genes and showed deregulation of osteogenic markers which could be an initial step for the onset of osteosarcoma.

骨肉瘤（OS）是一种影响儿童和青少年的骨恶性肿瘤。具有种系 RB1 突变的视网膜母细胞瘤 (RB) 患者在生命的第二个十年易患骨肉瘤。多项研究，特别是在小鼠中的研究，揭示了 RB1 在成骨中的作用。由于小鼠和人类之间的视网膜母细胞瘤肿瘤发生存在物种特异性差异，因此我们认为值得探索 RB1 在成骨和骨肉瘤发病中的作用。在这项研究中，我们分析了生殖系RB患者眼眶脂肪组织来源的间充质干细胞在体外成骨过程中与生长突增相关的成骨标志物、抑癌基因和激素受体的时间基因表达，并将其与野生型进行比较RB1基因。具有杂合RB1突变的间充质干细胞表现出RB1和其他肿瘤抑制基因的表达减少，并表现出成骨标志物的失调，这可能是骨肉瘤发病的第一步。