N-acetylglucosamine 이 염증성 사이토카인 Interleukin-1 beta 에 의해 유발된 골흡수에 미치는 억제효과 = Effects of N-Acetylglucosamine on Suppression of Collagenolysis and Bone Resorption in Mouse Calvarial Osteoblasts

다국어 초록 (Multilingual Abstract)

We show that mouse calvarial osteoblasts in culture constitutively synthesize progelatinase-A. Then, mouse osteoblasts, which were stimulated by PTH, 1,25(OH)2D3, mononuclear cell conditioned medium (MCM) and IL-1 as bone resorption agents, showed increased collagenolysis by producing the active gelatinase. However, treatment of indomethacin and dexamethasone significantly decreased those effects of collagenolysis in mouse osteoblastic cells. On the other hand, IL-1 in stimulating bone resorption was examined using fetal mouse long bone organ culture. IL-1 stimulated bone resorption and produced marked resorption when present simultaneously. Furthermore, when it was examined the effects of indomethacin and dexamethasone on the dose dependent responses of IL-1 α , indomethacin and dexametasone produced a rightward shift in the IL-1dose response curve. The results of in vitro cytotoxicities showed that N-acetylglucosamine have no any cytotoxicities in concentrations of 1-200 yg/ml and furthermore there is no any cytotoxicity even in concentration of 300 yg/ml on mouse calvarial bone cells. N-acetylglucosamine had Protective activity against PTH (2 units/ml), or MCM (5%, v/v), or IL-1 α (1 ng/ml) or 1,25(OH) 2D3 (10 ng/ml), IL-1 α and IL-1β-induced collagenolysis in the mouse calvarial cells. Pretreatment of theN-acetylglucosamine for 1 h, which by itself had little effect on cell survival, did not enhance the collagenolysis, nor significantly reduced the collagenolysis by pretreatment. Furthermore, the medicinal extracts were shown to have the protective effects against collagenolysis induced by IL-1 α and IL-1 β. Pretreatment of the extracts for 1 h significantly reduced the collagenolysis. Interestingly, the N-acetylglucosamine were shown to have the inhibiting effects against gelatinase enzyme and prosseing activity induced by the bone resortion agents of PTH, 1,25(OH)2D3, IL-1 β and IL-1 α , with strong protective effect in pretreatment with the extracts. JV-acetylglucosamine were shown to have the inhibiting effects against IL-1 α - and IL-1 β -stimulated bone resorption and the effect of the pretreatment with a various concentrations of the medicinal extracts were significant. The inhibition extent and phenomena of IL-1-stimulated bone resorption by nonsteroidal anti-inflammatory agents of indomethacin and dexamethasone were similar to those obtained by H-acetylglucosamine treatment in the mouse calvarial tissue culture system. These results indicated that the N-acetylglucosamine are highly stable and applicable to clinical uses in osteoporosis.