Eucommia ulmoides Oliver polysaccharide stimulates bone formation by improving osteoblast differentiation via ERK/BMP-2/SMAD signaling

Abstract Osteoporosis (OP) is a metabolic disease characterized by low bone mineral mass owing to osteoblast dysfunction. Eucommia ulmoides Oliver (EuO) is a Chinese herbal medicine traditionally used to treat OP. Here, a polysaccharide purified from the EuO cortex (EuOCP3) was administered to OP mice constructed with dexamethasone (Dex) to investigate its anti-OP activity. EuOCP3 significantly improved Dex-induced bone microarchitecture destruction, increased osteoblast numbers and surface, and stimulated an increase in the expression of osteoblast differentiation markers in the femurs of OP mice. Furthermore, EuOCP3 was applied to MC3T3-E1 cells to further explore its effects on osteoblast differentiation. EuOCP3 significantly promoted osteoblast differentiation and increased the level of phosphorylated extracellular signal-regulated kinase1/2 (ERK1/2) and SMAD1/5/8 without influencing cell proliferation. The EuOCP3-mediated enhancement of osteoblast differentiation-related proteins and phosphorylated SMAD1/5/8 expression levels was strongly suppressed by an ERK inhibitor (PD98059), which confirmed the critical role of ERK signaling in EuOCP3-induced osteoblast differentiation. In summary, EuOCP3 can stimulate bone formation by improving osteoblast differentiation via ERK/BMP-2/SMAD signaling, indicating the potential use of EuOCP3 as a functional ingredient in food products for anti-OP treatment.