Department of Orthopaedic Surgery, Center for Tissue Regeneration and Repair, University of California , Sacramento, California.
Tissue Eng Part A. 2013 Dec;19(23-24):2638-44. doi: 10.1089/ten.TEA.2013.0047. Epub 2013 Aug 30.
Superficial zone protein (SZP) functions as a boundary lubricant in articular cartilage and decreases the coefficient of friction. As lubrication of articular cartilage is critical for normal joint function, the ability to secrete SZP at the surface of tissue-engineered cartilage is a prerequisite for optimal lubrication. Synovium-derived mesenchymal stem cells (MSCs) are thought to be an attractive cell source for cartilage regeneration. However, optimization of a three-dimensional environment is necessary for tissue engineering. In this study, we investigated whether synovial explants, which would preserve the physiologic microenvironment for MSCs therein, have the potential of SZP secretion after chondrogenic differentiation by treatment with transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7). Immunostaining and enzyme-linked immunosorbent assay analysis demonstrated that synovial explants can synthesize and secrete SZP following chondrogenic differentiation in response to TGF-β1 and BMP-7. Interestingly, the combined treatment with TGF-β1 and BMP-7 or treatment first with TGF-β1 followed by BMP-7 was more effective than other treatment groups in both chondrogenic differentiation and SZP secretion. In conclusion, synovial explants represent not only a superb source of progenitors/stem cells for the regeneration of the surface zone of articular cartilage, but also a useful model system for the in vitro differentiation into mature articular cartilage phenotypes in response to morphogens for tissue engineering of articular cartilage.
表层蛋白 (SZP) 作为关节软骨的边界润滑剂,可降低摩擦系数。由于关节软骨的润滑对于正常关节功能至关重要,因此组织工程软骨表面能够分泌 SZP 是实现最佳润滑的前提条件。滑膜来源的间充质干细胞 (MSCs) 被认为是软骨再生的有吸引力的细胞来源。然而,为了进行组织工程,需要对三维环境进行优化。在这项研究中,我们研究了滑膜外植体是否具有在转化生长因子-β1 (TGF-β1) 和骨形态发生蛋白-7 (BMP-7) 作用下分化为软骨后分泌 SZP 的潜力,因为滑膜外植体可以保留其中 MSCs 的生理微环境。免疫染色和酶联免疫吸附试验分析表明,滑膜外植体在响应 TGF-β1 和 BMP-7 进行软骨分化后可以合成和分泌 SZP。有趣的是,与其他处理组相比,TGF-β1 和 BMP-7 的联合处理或首先用 TGF-β1 处理然后用 BMP-7 处理在软骨分化和 SZP 分泌方面更有效。总之,滑膜外植体不仅是关节软骨表面区域再生的祖细胞/干细胞的绝佳来源,而且还是对形态发生因子进行体外分化为成熟关节软骨表型的有用模型系统,可用于关节软骨的组织工程。