Effects of total glucosides of paeony on co-cultured osteoclasts and its mechanisms / 中国药理学通报

ABSTRACT

s:Aim To study the effects of total gluco-sides of paeony ( TGP) on the differentiation of co-cul-tured osteoclasts and the mechanisms of how TGP influ-ences the osteoclasts. Methods The synovial fibro-blasts and monocytes of peripheral blood in adjuvant-induced arthritic rats were separated and co-cultured to induce osteoclasts. The cells were treated with different TGP dosages (5, 50, 500, 5 000 mg·L-1 , and 50 g ·L-1 ) for 48 h. The proliferation, the TRAP activi-ty, and the bone resorption of osteoclasts were ob-served. The levels of IL-1,TNF-α,M-CSF and RANKL in the supernatants of osteoclasts were detected using ELISA. Meanwhile, the expression of ERK, JNK and p38 was detected by real time PCR. Results The ex-periments revealed that 50, 500, 5 000 mg·L-1 TGP inhibited the osteoclast growth, the TRAP activity, and the resorption pit area in a dose-dependent manner. TGP also inhibited the levels of IL-1 , TNF-α, M-CSF and RANKL in the supernatants and the expression of ERK, JNK and p38 in osteoclasts. The appropriate concentrations were 50 mg·L-1 to 5 000 mg·L-1 and had dose-dependent effects within this range. Conclu-sions TGP regulates the differentiation and activity of co-cultured osteoclasts. The effects of TGP are related to its inhibiting the cytokines secretion of synovial fi-broblasts and the activity of MAPK pathways.