Icariin: A Potential Osteoinductive Compound for Bone Tissue Engineering

Abstract

To effectively treat bone diseases using bone regenerative medicine, there is an urgent need to develop safe and cheap drugs that can potently induce bone formation. Here, we demonstrate the osteogenic effects of icariin, the main active compound of Epimedium pubescens. Icariin induced osteogenic differentiation of preosteoblastic cells. The combination of icariin and a helioxanthin-derived small compound synergistically induced osteogenic differentiation of MC3T3-E1 cells to a similar extent to bone morphogenetic protein-2. Icariin enhanced the osteogenic induction activity of bone morphogenetic protein-2 in a fibroblastic cell line. Mineralization was enhanced by treatment with a combination of icariin and calcium-enriched medium. The in vivo anabolic effect of icariin was confirmed in a mouse calvarial defect model. Eight-week-old male C57BL/6N mice were transplanted with icariin-calcium phosphate cement (CPC) tablets or CPC tablets only (n = 5 for each), and bone regeneration was evaluated after 4 and 6 weeks. Significant new bone formation was observed in the icariin-CPC group at 4 weeks, and the new bone thickness had increased by 6 weeks. Obvious blood vessel formation was observed in the icariin-induced new bone. Treatment of senescence-accelerated mouse prone 1 and senescence-accelerated mouse prone 6 models further demonstrated that icariin was able to enhance bone formation in vivo. Therefore, icariin is a strong candidate for an osteogenic compound for use in bone tissue engineering.

Icariin may benefit the mesenchymal stem cells of patients with steroid-associated osteonecrosis by ABCB1-promoter demethylation: a preliminary study

“…Icariin, extracted from Herba Epimedii, has been proved to play an important role in bone anabolism [22,23,[29][30][31]. Although some of the underlying molecular mechanisms have been partly clarified by previous studies, the relevance of icariin and epigenetic modification remains to be elucidated.…”

Icariin: a potential promoting compound for cartilage tissue engineering

“…Icariin have been proved that is an efficient promoting compound for the anti-osteoporosis, the restoration of bone defects and the bone tissue engineering 11,18,29 . Cartilage has similar embryogenesis with bone, and the promoting of the icariin for the bone regeneration may base on the enhancing of the endochondral ossification 18 .…”

“…Icariin could regulate the anabolism of osteoblasts through the up-regulation of BMP-4, BMP-2 and SMAD4 expression 15e17 . In bone tissue engineering, icariin has been proved an efficient accelerator 18,19 . Some reports indicated that the osteoinductive effect of icariin in vivo might be expressed through the process of endochondral ossification 19 .…”

Icariin stimulates MC3T3-E1 cell proliferation and differentiation through up-regulation of bone morphogenetic protein-2

“…Icariin is a strong candidate for an osteogenic compound for use in bone tissue engineering (12). A previous study showed that icariin could induce bone marrow stromal cell proliferation (7).…”