| Objectives: Postmenopausal osteoporosis is a common disease which is confirmed by epidemiology. It belongs to the type of high turnover rate, and the main cause is the deficiency of estrogen. However, osteoporosis seldom occurs among children and adolescent with low concentration of estrogen in serum and high rate of bone turnover. This paradoxical fact indicates that there are others reasons aside the deficiency of estrogen in osteoporosis pathogenesis. It's possible that these reasons break the balance between the bone formation and the bone absorption. When absorption exceed that of formation, bone lose and osteoporosis occurs.Recent studies showed that advanced glycosylation end products (AGEs) played an important role in osteoporosis pathogenesis, which were formed spontaneously in proteins by a non-enzymatic reaction with sugar, characterized by specific fluorescence and cross-linked structures. It is necessary for normal tissue remodeling and homeostasis. But excessive formation and accumulation of AGEs will induce a series of pathologic changes. On the one hand, cross-linking will occurs between the proteins modified by AGEs, whichaltered the physiological function of proteins. On the other hand, by the combination of AGEs with their receptors on surface of cell membrane, AGEs stimulated these cells to synthesis and secrete a series of cytokines and growth factors affecting the proliferation and differentiation of target cells in tissues and stimulating the synthesis and release of the extracellular matrix, which lead to indirect pathogenic alternation. AGE-formation on collagen resulted in increasing collagen insolubility and cross-linking, which altered the microarchitecture and functional properties of the collagen. In addition, AGEs can stimulate monocyte and osteoblast to produce some cytokines such as IL-K IL-6^ TNF and so on,which associated with bone absorption. It was reported that AGEs play an important role in senile and diabetic osteoporosis. Ageing and carbohydrate metabolism disorder were important causes of accumulation of AGEs, while menopause can result in carbohydrate metabolism disorder.Type I collagen is the main component of extracellular matrix in bone, which is up to 90%. It is the substance to keep elasticity and tenacity of bone, and is the site where hydroxyapatite deposit. Many studies showed that deficiency or degeneration of type I collagen had a close relationship with osteoporosis and bone loses. The function of collagen altered when it was modified by AGEs, and the incidence of bone lose and osteoporosis rises. In this study, we haveinvestigated the effect of AGEs on type I collagen synthesis in ovariectomized rats or in rat calvaria-derived osteoblast, in order to explore the role of AGEs in osteoporosis pathogenesis.Method:Thirty-nine Sprague-Dawley rats (ten months of age) were divided randomly into three groups: OVX group(OVX): ovariectomized; OVX+AG group (OVX+AG): ovariectomized and administered with aminoguanidine (0.1% in drinking water ); Sham group(Sham):resected a little of fat instead of ovaries. After 3 months, all rats had a fast of 24 hours. Urine was collected. All rats were killed after drawing blood from the femur aorta. The blood allowed to clot, centrifuged and the serum was used for determination of serum Ca, P, ALP et al. Left femurs and tibias for measurement of bone mineral density. Right tibias were defleshed and stored at -70 until used for determination of type I collagen mRNA by RT-PCR. Right femurs were dealed with the same method for determination of collagen-linked fluorescence. AGE-protein was prepared by means of the incubation of BSA with glucose. Cells were incubated for different periods of times after exposure to different doses of BSA or AGE-BSA to assess time-dependent and dose-dependent pattern AGE-BSA effect. Then selecting the doses and time that AGE-BSA has maximal effect, RT-PCR was used to observe the effects of AGE-BSA on expression of type I collagen mRNA.Result:1. Biochemical marker in serum and in... |
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