骨肉瘤是起源于骨骼的高度恶性肿瘤，其发病率在原发性骨恶性肿瘤中居首位。脂联素是脂肪细胞分泌的一种脂肪因子，近年研究表明脂联素与恶性肿瘤的发生发展起着密切负相关作用，但其具体机制目前尚不明确。我们前期工作发现脂联素在骨肉瘤患者血清中表达水平显著下降，其受体在骨肉瘤组织亦有特异性表达，同时脂联素可随时间和浓度改变激活mTOR上游信号分子AMPK，从而抑制mTOR的表达，提示其可能通过调节骨肉瘤组织细胞中的mTOR信号途径发挥作用,据此提出假设脂联素通过mTOR信号通路抑制骨肉瘤的发生发展。我们将用骨肉瘤细胞系（SaOS-2，MG-63）以及脂联素基因敲除小鼠、成骨细胞特异性Rheb1基因敲除小鼠以及人体骨肉瘤组织活检，从离体、在体以及人体三个层面阐明脂联素对于骨肉瘤mTOR信号通路的作用及机制。该研究将为骨肉瘤的的发生和发展提供重要信息，为临床骨肉瘤的治疗提供新的思路和药物新靶点。

Osteosarcoma is a major kind of primary bone malignant tumor. Adiponectin is one of the significant adipocytokines secreted by adipocytes, which is ubiquitously involved in processes including metabolism. Recent studies have demonstrated that adiponectin played a negative role in regulating the occurrence and development of malignant tumors, yet the underlying mechanisms require further exploration. Our preliminary data showed that expression of serum adiponectin was significantly impaired in patients with osteosarcoma, while the adiponectin receopor (AdipoR1) was specifically expressed in human osteosarcoma tissue. We also found that AMPK，as one of the upregulation signaling of mTOR pathway, was enhanced with increased adiponectin concentration or stimulus duration, whereas that the expression of mTOR pathway was suppressed in a similar time- and concentration-dependent way. Meantime,we can not rule out the possible effect of PI3K/Akt/mTOR axis as it has been proved to be a classical upregulation signaling of mTOR pathway. Therefore, we hypothesize that adiponectin negatively regulates the occurrence and development of osteosarcoma through mTOR signaling pathways. We will use various research strategies, including osteosarcoma cell lines(SaOS-2, MG-63), adiponectin whole body knockout mice and Rheb1 osteoblast-specifically knockout mice, and human osteosarcoma tissue, to study the mechanism of regulation on osteosarcoma by adiponectin, and to study the effects of mTOR pathway both in vitro and in vivo. Our study will provide important information for the mechanisms of osteosarcoma proliferation and development, which could provide new thoughts and new drug targets for the clinical treatment of osteosarcoma.