Icariin promotes extracellular matrix synthesis and gene expression of chondrocytes in vitro

To effectively treat articular cartilage defect with tissue engineering there is an urgent need to develop safe and cheap drugs that can substitute or cooperate with growth factors for chondrogenesis promotion. Here, we demonstrate the chondrogenic effect of icariin, the major pharmacological active constituent of Herb Epimedium (HEP). Rabbit chondrocytes were isolated from articular cartilage and cultured in vitro with different concentrations of icariin. Icariin at concentrations under 1 × 10⁻⁵ M showed low cytotoxicity toward chondrocytes, but icariin at 5 × 10⁻⁵ M inhibited the proliferation of chondrocytes. Icariin hardly affected the cell morphology with concentrations ranging from 1 × 10⁻⁷ M to 5 × 10⁻⁵ M. However, the higher concentration of icariin produced more extracellular matrix (ECM) synthesis and expression of chondrogenesis genes of chondrocytes. Indeed, the promotion of icariin on the synthesis of glycosaminoglycans (GAGs) and collagen of chondrocytes, and finally exerting a potent chondrogenic effect, might be due to its ability to up-regulate the expression of aggrecan, collagen II and Sox9 genes and to down-regulate the expression of the collagen I gene of chondrocytes. These preliminary results imply that icariin might be an effective accelerant for chondrogenesis and that icariin-loaded biomaterials might have the potential for cartilage tissue engineering. 1 × 10⁻⁵ M may be a suitable concentration of icariin with chondrogenic effect for tissue engineering.