Icariin Accelerates Fracture Healing via Activation of the WNT1/β-catenin Osteogenic Signaling Pathway

摘要

Background: Icariin has been shown to enhance bone formation.Objective: The present study aimed to investigate whether icariin also promotes bone fracture healingand its mechanisms.Methods: First, we isolated and cultured rat bone marrow stromal cells (rBMSCs) with icariincontainingserum at various concentrations (0%, 2.5%, 5% and 10%) and then measured alkalinephosphatase (ALP) activity and the expression of Core-binding factor, alpha 1 (Cbfα1), bone morphogeneticprotein-2 (BMP-2) and bone morphogenetic protein-4 (BMP-4) in the rBMSCs. Second, weestablished a model of fracture healing in rats and performed gavage treatment for 20 days. Then, wedetected bone biochemical markers (ELISA kits) in the serum, fracture healing (digital radiography,DR), and osteocalcin expression (immunohistochemistry).Results: Icariin treatment increased ALP activity and induced the expression of Cbfα1, BMP-2 andBMP-4 in rBMSCs in a dose-dependent manner. In addition, Icariin increased the serum levels of osteocalcin(OC), bone-specific alkaline phosphatase (BAP), N-terminal telopeptides of type I collagen(NTX-1), C-terminal telopeptide of type I collagen (CTX-1) and tartrate-resistant acid phosphatase 5b(TRACP-5b); promoted osteocalcin secretion at the fracture site; and accelerated fracture healing.Conclusions: Icariin can promote the levels of bone-formation markers, accelerate fracture healing,and activate the WNT1/β-catenin osteogenic signaling pathway.