Fu Runqing, Han Fengxuan, Liu Lu, Yu Fei, Gui Zhipeng, Wang Xiaoting, Li Bin, Fang Bing, Xia Lunguo
Department of Orthodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
ACS Biomater Sci Eng. 2019 Apr 8;5(4):1907-1919. doi: 10.1021/acsbiomaterials.8b01168. Epub 2019 Mar 6.
Patients with cartilage damage have various discomforts, including pain, clicks, deformities, and dysfunction. Chondrocytes are a crucial component of cartilage restoration; however, their limited proliferative ability and degenerative specificity dramatically reduce their effectiveness. In the present study, the effects of leptin on chondrocyte proliferation, chondrogenic and secretion marker gene expression, and chondrocyte cartilage matrix component secretion were evaluated in vitro. The roles of the mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) signaling pathways in these processes were also investigated. More importantly, a leptin sustained release system was developed using a hydrogel with calcium alginate microspheres and was transplanted into cartilage defects in rabbit femurs to analyze the effect of leptin on promoting cartilage restoration. The results showed that leptin promoted cell proliferation and chondrocyte gene expression in a dose-dependent manner, and a concentration of 100 ng/mL leptin had the greatest effect. The activation of the P38 and AKT signaling pathways might be responsible for these effects. An improved in vivo restoration outcome was observed in the leptin sustained release group compared with the control group. These results suggest that leptin could be used as a suitable drug for cartilage restoration.
软骨损伤患者会出现各种不适症状，包括疼痛、弹响、畸形和功能障碍。软骨细胞是软骨修复的关键组成部分；然而，它们有限的增殖能力和退化特异性极大地降低了其有效性。在本研究中，在体外评估了瘦素对软骨细胞增殖、软骨形成和分泌标志物基因表达以及软骨细胞软骨基质成分分泌的影响。还研究了丝裂原活化蛋白激酶（MAPK）和蛋白激酶B（AKT）信号通路在这些过程中的作用。更重要的是，使用含有海藻酸钙微球的水凝胶开发了一种瘦素缓释系统，并将其植入兔股骨的软骨缺损中，以分析瘦素对促进软骨修复的作用。结果表明，瘦素以剂量依赖的方式促进细胞增殖和软骨细胞基因表达，100 ng/mL的瘦素浓度效果最佳。P38和AKT信号通路的激活可能是这些作用的原因。与对照组相比，瘦素缓释组在体内的修复效果有所改善。这些结果表明，瘦素可作为一种适用于软骨修复的药物。
