Parthenolide ameliorates glucocorticoid-induced inhibition of osteogenic differentiation and osteoporosis by activating ERK signaling pathway.

Background: Parthenolide (PTL) is a natural sesquiterpene lactone that possesses significant effects on stimulating osteoblast differentiation. The present study focused on the potential of PTL in the treatment of glucocorticoid-induced osteoporosis (GIOP).

Methods: MC3T3-E1 cells were treated with dexamethasone (DEX; 10 µM) or/and PTL (5, 10, and 20 µM). The changes in osteogenic differentiation were analyzed by conducting ALP and Alizarin Red staining and assessing the levels of osteogenic markers (Runx2, Osx, and OPN). PTL (3 and 10 mg/kg/day) was injected into rat models of GIOP induced by DEX. Bone formation was analyzed by assessing the levels of bone turnover markers (ALP, TRAP, OCN, and CTx) in the serum and osteoblast differentiation markers (BMP2 and Runx2) in the femurs. The pathological changes of the femurs were determined by H&E staining. Bone mass and osteoblast numbers in the femurs were measured. Western blotting evaluated ERK phosphorylation in vitro and in vivo.

Results: PTL promoted osteogenic differentiation and enhanced the levels of Runx2, Osx, OPN, and ERK phosphorylation in DEX-treated MC3T3-E1 cells. ERK inhibitor U0126 reversed the promoting effect of PTL on osteogenesis in DEX-treated MC3T3-E1 cells. After the administration of PTL in rat models of GIOP, the levels of ALP, TRAP, OCN, and CTx in the serum and the levels of BMP2, Runx2, and ERK phosphorylation in the femurs were restored. PTL increased trabecular bone number, reduced trabecular separation, and increased the number of osteoblasts in GIOP rat model.

Conclusions: Overall, PTL alleviates osteoporosis by promoting osteogenic differentiation via activation of ERK signaling.