Lead exposure inhibits osteoblastic differentiation and inactivates the canonical Wnt signal and recovery by icaritin in MC3T3-E1 subclone 14 cells.

Exposure to lead (Pb) poses a threat to human bone health, including changes in bone mineral composition and the inhibition of skeletal growth and bone maturation. However, little is known about how Pb directly affects osteoblasts. In this work, we found that sub-toxic Pb concentrations suppressed bone nodule formation and inhibited differentiation in MC3T3-E1 subclone 14 cells, as shown by decreased expression levels of the differentiation markers alkaline phosphatase (ALP), type 1 collagen (COL1), osteocalcin (OC), and runt-related transcription factor 2 (RUNX2). Moreover, Pb inactivated the canonical Wnt pathway by regulating key components, such as Wnt3a, Dkk-1, pGSK3β, and β-catenin. Icaritin (ICT), a hydrolytic product of icariin from the genus Epimedium, attenuates the inhibitory effect of Pb on osteoblastic differentiation, as well as activate the canonical Wnt signal pathway. Taken together, the results suggest ICT as a potential bone protectant that may be used to prevent bone damage caused by Pb and can activate the canonical Wnt signal pathway.