Genistein, a major phytoestrogen of soy, is considered a potential drug for prevention and treatment of postmenopausal osteoporosis. The aim of the present study was to compare the effects of genistein, estradiol and raloxifene on the skeletal system in vivo and in vitro. Genistein (5 mg/kg), estradiol (0.1 mg/kg) or raloxifene hydrochloride (5 mg/kg) were administered daily by a stomach tube to mature ovariectomized Wistar rats for 4 weeks. Bone mass, mineral and calcium content, macrometric parameters and mechanical properties were examined. Also the effects of genistein, estradiol and raloxifene (10-9-10-7 M) on the formation of osteoclasts from neonatal mouse bone marrow cells and the activity of osteoblasts isolated from neonatal mouse calvariae were compared. In vivo, estrogen deficiency resulted in the impairment of bone mineralization and bone mechanical properties. Raloxifene but not estradiol or genistein improved bone mineralization. Estradiol fully normalized the bone mechanical properties, whereas genistein augmented the deleterious effect of estrogen-deficiency on bone strength. In vitro, genistein, estradiol and raloxifene inhibited osteoclast formation from mouse bone marrow cells, decreasing the ratio of RANKL mRNA to osteoprotegerin mRNA expression in osteoblasts. Genistein, but not estradiol or raloxifene, decreased the ratio of alkaline phosphatase mRNA to ectonucleotide pyrophosphatase phosphodiesterase 1 mRNA expression in osteoblasts. This difference may explain the lack of genistein effect on bone mineralization observed in ovariectomized rats in the in vivo study. Concluding, our experiments demonstrated profound differences between the activities of genistein, estradiol and raloxifene towards the osseous tissue in experimental conditions.
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The bone tissue remodelling is a relatively slow process. In physiologically "normal" conditions, it tends towards the state of remodelling equilibrium. In the state of final remodelling equilibrium, the strain energy reaches its minimum. In the life of each human being, the bone tissue passes through the repeating limit cycles of its development, functioning and destruction. The paper presented is aimed at the biomechanochemical processes within one limit cycle of bone remodelling using the stoichiometric equations and kinetic equations. Each limit cycle of the bone tissue remodelling (in its assumed volume element) consists of several stages, in which the biochemical reactions are proceeding in a highly intensive way, and of several periods in which the tissue is in weakly steady states (i.e.. the biochemical reactions are very slow or they almost do not take place). Generally, throughout the life of a human, a bone tissue is several times in the principal weakly steady state, i.e., in such a state in which the long-term remodelling equilibrium is reached. This period lasts for several years (roughly for 6-8 years) in the life of an adult human in his/her productive age, while in the life of a child this period is shorter. Figuratively speaking, the stages of the bone tissue remodelling (during one limit cycle) can be compared to the tissue "childhood and maruraiion" (i.e., n stage of remodelling - apposition of the tissue), and "aging-demise" (I stage of remodelling - resorption). One limit cycle of the bone tissue life (out of the series of the subsequent periodic limit cycles) that is characterized by the bone tissue development, functioning and destruction (in the unit volume element) can be synoptically, and in the real time, described by four stages. The limit cycle is a close trajectory of solution of kinetic equations of bone remodelling. The bone tissue (in its unit volume element) passes through the repeating harmonic limit cycles (i.e., the stable periodic processes) of its development and destruction.
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Bone remodelling is a very complicated process that can be characterised as close relationship of biomechnical effects and biomechanical reactions. It is not possible to give an exact definition of the bone remodeling if we take into consideration the aspects related merely to biomechanics or to biochemistry. Biomechanical processes in a remodelled bone tissue depend on the dominant force and moment effects or on the stress and strain state of the tissue. The stress (strain) tensors initiate and govern the rate of biochemical remodelling processes. The paper presented deals with fundamental stoichiometric equations of bone remodelling, kinetic equations of remodelling and rate constants of remodelling. The rates of bone remodelling depend on mechanical effects or on stress (strain) tensors. The spherical stress tensor controls the rate of biomechanical remodelling reactions, while the deviator of a stress (strain) tensor initiates biomechanical reactions. The micro-strains cause the flow of a liquid in the extra-celluar space of osteocytes and initiate the receptor activity of integrins A,B, The micro-strains of a mineralised matrix and the flow of an extra-cellular liquid result, for example in the production of prostaglandin E2 and in the subsquent resorption of a bone tissue.
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