Potent inhibitory effects of anthraquinone compounds from Morinda officinalis on in vitro osteoclastic bone resorption

Abstract

The root of Morinda officinalis F.C.How has been shown to exert protective effects against bone loss in sciatic neurectomy and ovariectomy rats [1–3], and anthraquinones from this plant may contribute to this activity [4]. In the present study, we investigated the effects of 1, 3, 8-trihydroxy-2-methoxy-anthraquinone (1), 2-hydroxy-1-methoxy-anthraquinone (2), and rubiadin (3) from the plant the in vitro bone resorbing activity and mechanism. In the coculture system of osteoblast and bone marrow cells, the compound 1, 2 and 3 decreased the formation of bone resorption pit, the number of multinucleated osteoclasts, tartrate resistant acid phosphates and cathepsin K activity of osteoclasts within the dose range of 0.1˜10µmol/L (P<0.01). Further, the compound 1, 2 and 3at concentration of 1µmol/L improved the ratio of mRNA and protein expression of OPG and RANKL in osteoblasts (P<0.01 for compound 1 and 2; P<0.001 for compound 3). In osteoclasts induced from bone marrow cells with MCSF and RANKL, the compound 1, 2 and 3at concentration of 1µmol/L enhanced the apoptosis of osteoclast (P<0.01), disturbed the JNK and NF-κB signal pathway (P<0.01), reduced the expression of calcitonin receptor (P<0.05 for compound 1; P<0.01 for compound 2 and 3) and carbonic anhydrase II (P<0.05 for compound 1 and 3; P<0.01 for compound 2). Therefore, the findings of the present study demonstrate that anthraquinones from Morinda officinalis is an inhibitor of bone resorption, and potentially explaining some of reported inhibitory effects on bone loss.