Amarogentin promotes osteoblast differentiation in oestrogen-deficiency-induced osteoporosis rats by modulating the Nrf-2/MAPK/ERK signalling pathway.

INTRODUCTION

The beneficial effect of amarogentin in the management of osteoporosis was determined using and methods.

MATERIAL AND METHODS

Experimental osteoporosis was induced in rats via bilateral ovariectomy. Rats were then treated for 5 weeks with amarogentin (50 and 100 mg/kg, p.o.). The levels of several biochemical markers of bone resorption and formation as well as bone mineral density (BMD) were measured in the rat serum. Isolated rat bone tissues were analysed using western blot assays. In the study, MG63 human osteoblasts were treated with amarogentin (0-100 μg/ml), after which alkaline phosphatase activity and osteoblast proliferation were evaluated. Osteoblasts treated with amarogentin and inhibitors of extracellular signal-regulated kinase (ERK) were further examined via western blotting.

RESULTS

In the rat model of oestrogen-deficiency-induced osteoporosis, BMD was significantly enhanced ( < 0.01) and levels of inflammatory cytokines were reduced in amarogentin-treated animals vs. the controls. Amarogentin treatment also attenuated the altered levels of osteocalcin, C-telopeptide of type 1 collagen, procollagen type I N-terminal propeptide, and bone-specific alkaline phosphatase, and the altered expression of Akt, Nrf-2, ERK, and nuclear factor-κB p65 in the serum of rats with osteoporosis. In the study, amarogentin treatment enhanced alkaline phosphatase activity and osteoblast proliferation compared to the non-treated control. Amarogentin treatment alone enhanced the expression of p-ERK compared to treatment with an amarogentin + ERK inhibitor.

CONCLUSIONS

Both the and the studies demonstrated the protective effect of amarogentin against oestrogen-deficiency-induced osteoporosis in rats. The mechanism seems to involve the amarogentin-mediated enhancement of osteoblast differentiation via the Nrf-2/MAPK/ERK signalling pathway.