Induction of chondrogenesis and expression of superficial zone protein in synovial explants with TGF-β1 and BMP-7.

Abstract

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.