《生命科学》 2016, 28(8): 921-927

骨和软骨干细胞的分化调控与细胞治疗

徐佳佳1，干耀恺1，童文学1，李　姣1，戴尅戎1*，张晓玲1，2*

(1 上海交通大学医学院附属第九人民医院骨科，上海市骨科内植物重点实验室，上海 200011；2 上海交通大学医学院附属新华医院骨科，上海 200092)

摘　要：摘　要：干细胞分化调控和细胞治疗为相关的骨关节疾病提供了新颖且有效的治疗策略。张晓玲课题组研究发现，地塞米松(Dexamethasone， Dex) 可以使C/EBPα 启动子甲基化，从而将骨髓间充质干细胞(bone marrow mesenchymal stem cells， BMMSCs) 由成骨分化转向成脂分化。LiCl 激活的Wnt/β-catenin 通路可以救援Dex 对C/EBPα 启动子的甲基化和成骨细胞/ 脂肪细胞的分化平衡，从而为地塞米松诱导的骨质疏松症提供了一个有效的治疗靶点。此外，张晓玲课题组发现了一个有趣的现象，关节软骨干细胞(articular cartilage stem cells， ACSCs) 在骨关节炎(osteoarthritis， OA) 早期阶段被激活，表现出短暂的增殖反应和尝试自我修复。而IL-1β 能有效激活NF-κB 通路，削弱ACSCs 的损伤响应。NF-κB 通路抑制剂可以援救ACSCs 的软骨形成，诱导软骨再生，保护关节软骨损伤。同时，张晓玲课题组开发了一种基于富集骨髓间充质干细胞复合多孔β- 磷酸三钙(β-tricalcium phosphate， β-TCP) 的新的安全、有效的微创临床细胞治疗法，该细胞疗法能促进骨骼和软骨的修复和再生，避免了一些与细胞扩增有关的伦理问题，使得临床应用变得更便宜和更方便。

The differentiation regulation and cytotherapy based on stem cells in bone and cartilage

XU Jia-Jia1， GAN Yao-Kai1， TONG Wen-Xue1， LI Jiao1， DAI Ke-Rong1*， ZHANG Xiao-Ling1，2*

(1 Shanghai Key Laboratory of Orthopaedic Implant， Department of Orthopaedics， Shanghai Ninth People’s Hospital， Shanghai Jiao Tong University School of Medicine (SJTUSM)， Shanghai 200011， China; 2 Department of Orthopedic Surgery， Xinhua Hospital， Shanghai Jiao Tong University School of Medicine (SJTUSM)， Shanghai 200092， China)

Abstract: Abstract: The differentiation regulation and cytotherapy based on stem cells will provide useful new therapeutic strategy for related bone and joint disease. For the last several years， we found that Dexamethasone (Dex) shifts bone marrow mesenchymal stem cells (BMMSCs) from osteoblasts to adipocytes by C/EBPα promoter methylation. Wnt/β-catenin pathway activation by LiCl rescues the effect of Dex on C/EBPα promoter methylation and osteoblast/adipocyte balance， thus providing a useful therapeutic target for Dex-induced osteoporosis. We found an interesting phenomenon that articular cartilage stem cells (ACSCs) were activated and exhibited a transient proliferative response in early osteoarthritis (OA) as an initial attempt for self-repair， whereas IL-1β can efficiently activate the NF-κB pathway and potently impair the responsiveness of ACSCs. The NF-κB pathway inhibitor rescued the ACSCs chondrogenesis， induced cartilage regeneration， and protected articular cartilage from injury. We developed a new safety， effectiveness， and minimal invasiveness clinical cytotherapy method based on enriched BMSCs combined with porous β-tricalcium phosphate (β-TCP). The cytotherapy could promote bone and cartilage repair and regeneration， it avoids some ethical problems associated with cell expansion and becomes both less expensive and more convenient for clinical usage.