Study On Alterations Of Induction On Osteoblasts By Bone Morphogenetic Protein-2 Under Simulated Weightlessness

While human exploit the space taking advantage of modern technology, we also have encountered many unexpected problems. Among them the most important and urging one is how to sustain man's life and function effectively in space. Osteoporosis induced by microgravity, one of the serious diseases acquired in space, is now becoming a more and more absorbing target in the space medicine field. Exposure to microgravity or weightlessness will cause a series of malignant alterations to human's skeleton system, including loss of bone mass and bone mineral, declines in bone mechanical function and negative calcium balance which all cannot ameliorate automatically at all. A long period of time staying in space may lead to bone fracture, unstable in inner environment balance, stone formingin urine system and decline in muscle function as a result, which make great challenges toward realizing our dreams of conquering space. Although scientists have achieved fruitful success during investigation of pathogenesis of osteoporosis under microgravity and finding effective countermeasures, several difficult problems are remained unsolved yet.Until now it's well recognized that the bone loss under microgravity is caused by a malfunction in focal area concerning many complex modulation systems. Studies have confirmed that the decline of bone formation is mainly responsible for the bone loss induced by microgravity or weightlessness. So the mutual reaction between osteoblasts and their regulators-relative growth factors has now become a focus in this field, which will also be one of the break points in finding effective countermeasures. Bone morphogenetic proteins, as a proteins family which have remarkable stimulation both on bone formation and on bone absorption, are studied profoundly and exclusively in recent years. But they are seldom concerned in studies of osteoporosis induced by microgravity. In terms of this context we designed and carried out the experiment below in order to uncover the alterations on the induction of osteoblasts by BMP under simulated weightlessness and to explore the further pathogenesis in osteoporosis induced by simulated weightlessnes, expecting to find any possibilities of new countermeasures.1. Study on culture of osteoblasts from neonatal rat's calvaria in simulated weightlessness. Constructed cell model under simulated weightlessness by clinostat and confirmed the credibility by assessing the expression of biomarkers-alkaline phosphatase and osteocalcin.2. Addition of recombinant human BMP-2 into the culture media andobserved the alteration on the exact expression of ALP and osteocalcin under simulated weightlessness in different period of time.3. Addition of recombined human BMP-2 into the culture media and observed the alteration on the mRNA and protein expression of osteoprotegerin and osteoprotegerin ligand under simulated weightless -ness in different period of time.Results as follows.1. Under simulated weightlessness, the ALP expression of osteoblasts induced by BMP-2 was remarkably lower than that under normal gravity. No difference was found in expression of osteocalcin between groups under simulated weightlessness and the ones under normal gravity. The data indicated that the osteoblasts' osteogenic sensitivity against BMP-2 was lower than normal.2. Under simulated weightlessness or normal gravity conditions, BMP-2 induced osteoblasts to produce more OPG mRNA and inhibited the OPGL mRNA production.3. There's no significant difference in the expression of OPG mRNA and OPGL mRNA under simulated weightlessness or normal gravity. But simulated weightlessness inhibited both two factors' protein expression. The data indicated that there may be some posftranscriptional factors downregulating the protein expression of OPG and OPGL.4. The proportion of OPG mRNA compared with OPGL mRNA was increased remarkably in BMP-2 stimulating groups.5. There was no significant difference in the proportion between BMP-2 stimulating groups under simulat...