He Ruijun, Wang Baichuan, Cui Min, Xiong Zekang, Lin Hui, Zhao Lei, Li Zhiliang, Wang Zhe, Peggrem Shaun, Xia Zhidao, Shao Zengwu
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Centre for NanoHealth, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
Stem Cells Int. 2018 Jan 30;2018:3217895. doi: 10.1155/2018/3217895. eCollection 2018.
Link protein N-terminal peptide (LPP) in extracellular matrix (ECM) of cartilage could induce synthesis of proteoglycans and collagen type II in cartilaginous cells. Cartilage stem/progenitor cells (CSPCs), the endogenous stem cells in cartilage, are important in cartilage degeneration and regeneration. We hypothesized that LPP could be a stimulator for stem cell-based cartilage regeneration by affecting biological behaviors of CSPC.
CSPCs were isolated from rat knee cartilage. We evaluated the promoting effect of LPP on proliferation, migration, and chondrogenic differentiation of CSPCs. The chondrogenic differentiation-related genes and proteins were quantitated. Three-dimensional culture of CSPC was conducted in the presence of TGF-3 or LPP, and the harvested pellets were analyzed to assess the function of LPP on cartilage regeneration.
LPP stimulated the proliferation of CSPC and accelerated the site-directional migration. Higher expression of SOX9, collagen II, and aggrecan were demonstrated in CSPCs treated with LPP. The pellets treated with LPP showed more distinct characteristics of chondroid differentiation than those with TGF-3.
LPP showed application prospect in cartilage regeneration medicine by stimulating proliferation, migration, and chondrogenic differentiation of cartilage stem/progenitor cells.
软骨细胞外基质中的连接蛋白N端肽(LPP)可诱导软骨细胞合成蛋白聚糖和II型胶原蛋白。软骨干细胞/祖细胞(CSPCs)是软骨中的内源性干细胞,在软骨退变和再生中起重要作用。我们假设LPP可能通过影响CSPCs的生物学行为,成为基于干细胞的软骨再生的刺激因子。
从大鼠膝关节软骨中分离出CSPCs。我们评估了LPP对CSPCs增殖、迁移和软骨分化的促进作用。对软骨分化相关基因和蛋白质进行定量分析。在转化生长因子-β(TGF-3)或LPP存在的情况下进行CSPCs的三维培养,并对收获的微球进行分析,以评估LPP对软骨再生的作用。
LPP刺激CSPCs的增殖并加速其定向迁移。在用LPP处理的CSPCs中,SOX9、II型胶原蛋白和聚集蛋白聚糖的表达更高。与用TGF-3处理的微球相比,用LPP处理的微球表现出更明显的软骨样分化特征。
LPP通过刺激软骨干细胞/祖细胞的增殖、迁移和软骨分化,在软骨再生医学中显示出应用前景。