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The Effect Of Aging On The Expression Of Osteogenic And Adipogenic Factors And Nfic In Rats

Posted on:2018-08-21Degree:MasterType:Thesis
Country:ChinaCandidate:F C ZhangFull Text:PDF
GTID:2334330518951866Subject:Oral and clinical medicine
Abstract/Summary:PDF Full Text Request
There will be a series of irreversible degenerative changes in morphology and physiological function of organisms with aging, such as bone loss, bone microstructure changes and destruction, in contrast, the body's adipogenic ability increased, a large of ossium flava medulla being rich in fat growed in the marrow cavity. The alteration of the macroscopic appearance is regulated by the changes of the micro mechanism, including the signal pathway, the genetic gene, hormones and paracrine factors, among whtch, the most important factor is the intracellular signaling pathway and genetic gene.Multiple bone formation signal regulatory pathways have been found and confirmed, among which,the BMP-Smad signaling pathway plays an important role in osteogenic differentiation and bone formation. BMPs is the primary factor of this pathway, the gene mediates the body bone through a series of signal transduction pathway by transferring to the downstream genes. In this process, Runx2 and Osterixare are two osteoblast specific transcription factors. In other words,The BMPs signal are passed to the Runx2 and then transferred to the Osterix to guide the bone formation.Nuclear factor C (Nfic) is a member of the nuclear transcription factor I (NFI)family, previous studies have shown that Nfic mutations or deletionsResult in abnormal tooth roots. In a Nfic knockout rat experiment, foreign scholars proposed for the first time that in the BMP signaling pathway, the role of Runx2 gene in mediating the osteogenesis of Osterix is regulated by Nfic, Nfic is located in the downstream of Runx2 and upstream of Osterix. In addition,our preliminary studies have found that the expression of Nfic is consistent with the expression of osteogenic markers and BMP-Smad signaling pathway in the model of osteoporosis and diabetes.Adipogenesis is also regulated by multiple signaling pathways and transcription factors. The peroxisome proliferator binding protein gamma (PPAR-?)plays a major role, it can make the adipose tissue and bone tissue play a normal physiological function, its expression activity is a good indicator to adipogenic ability.In this study, we focused on the foll wings:? The biological changes of osteoblasts in aging state; ?The expression trend of osteogenic factors represented by BMP-Smad signaling pathway and the change of osteogenic markers;? The trend and correlation of the four genes especially Nfic of the nuclear factor family;? The effect of aging on the expression of adipogenic genes.The results showed that aging leads to the decrease of the osteogenic ability and the activity of osteoblasts gradually; the expression of osteogenic factors in BMP-Smad signaling pathway and AKP and BGP, which are derived from serum and bone tissue,were decreased. However, the first factor BMP-2 of the pathway was stable and even increased slightly ; there is a corresponding change in the expression of nuclear factor family genes, in which Nfic factor was consistent with the expression of BMP-Smad genes at the same time; the activity of PPARy derived from bone tissue decreased gradually with age.The results indicates that aging will lead to a decrease in the overall activity of BMP-Smad pathway, but the expression of BMP2 had no obvious change and even increased, therefore, the reduction of osteogenic activity is the result of multiple factors. The experiment indirectly reflects the consistency of Nfic and the BMP-Smad signaling pathway genes with the previous experimental results, supportting the conclusion that Nfic mediates osteogenic factors by BMP-Smad signaling pathway.PPARy derived from bone tissue declines, which may be effected by some anti adipogenic factors.
Keywords/Search Tags:Aging, osteogenic factor, Runx2, Osterix, PPAR?, cell cycle, growth index, nuclear factor ? C, superoxide dismutase, nitric oxide, osteocalcin, alkaline phosphatase
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