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Quantitative Proteomics Revealed the Changes of Pharmacodynamic Network of Bugu Shengsui Decoction Promoting Osteoblasts Proliferation

ABSTRACT: Insufficient osteogenesis is greatly essential to osteoporosis. Bugu Shengsui Decoction, a compound formula for osteoporosis, has significant clinical effects in the treatment of osteoporosis. Yet the detailed mechanisms are unclear. In this study, we first evaluated the pharmacological effects of Bugu Shengsui Decoction on bone metabolism, bone mineral density, bone morphology and biomechanics in ovariectomized rats. It also clarified the promoting effect of Bugu Shengsui Decoction on the proliferation and differentiation of osteoblasts. Based on the above results, we conducted quantitative proteomics research and a series of validation experiments, the results showed that PI3K-AKT signaling pathway and targets, such as Fn1, Col1a1, Col1a2, Col6a1, Col6a2, Col6a3, Rac1, Hsp90ab1, Hsp90b1, Ywhaz and Gnb2, were most relevant to the anti-osteoporosis efficacy of BGSSD. Summarily, our discoveries certify that Bugu Shengsui Decoction is an effective treatment for osteoporosis via PI3K-AKT.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Preosteoblast

DISEASE(S): Osteoporosis

SUBMITTER: Baoyu Qi

LAB HEAD: Jianye Dai

PROVIDER: PXD030275 | Pride | 2022-01-28

REPOSITORIES: Pride

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Project description:Background This work focuses on the computational modelling of osteomyelitis, a bone pathology caused by bacteria infection (mostly Staphylococcus aureus). The infection alters the RANK/RANKL/OPG signalling dynamics that regulates osteoblasts and osteoclasts behaviour in bone remodelling, i.e. the resorption and mineralization activity. The infection rapidly leads to severe bone loss, necrosis of the affected portion, and it may even spread to other parts of the body. On the other hand, osteoporosis is not a bacterial infection but similarly is a defective bone pathology arising due to imbalances in the RANK/RANKL/OPG molecular pathway, and due to the progressive weakening of bone structure. Results Since both osteoporosis and osteomyelitis cause loss of bone mass, we focused on comparing the dynamics of these diseases by means of computational models. Firstly, we performed meta-analysis on a gene expression data of normal, osteoporotic and osteomyelitis bone conditions. We mainly focused on RANKL/OPG signalling, the TNF and TNF receptor superfamilies and the NF-kB pathway. Using information from the gene expression data we estimated parameters for a novel model of osteoporosis and of osteomyelitis. Our models could be seen as a hybrid ODE and probabilistic verification modelling framework which aims at investigating the dynamics of the effects of the infection in bone remodelling. Finally we discuss different diagnostic estimators defined by formal verification techniques, in order to assess different bone pathologies (osteopenia, osteoporosis and osteomyelitis) in an effective way. Conclusions We present a modeling framework able to reproduce aspects of the different bone remodeling defective dynamics of osteomyelitis and osteoporosis. We report that the verification-based estimators are meaningful in the light of a feed forward between computational medicine and clinical bioinformatics Model is encoded by Ruby and submitted and curated to BioModels by Ahmad Zyoud

Project description:Large-scale transcriptional profiling has enormous potential for discovery of osteoporosis susceptibility genes and for identification of the molecular mechanisms by which these genes and associated pathways regulate bone maintenance and turnover. A potential challenge in the use of this method for the discovery of osteoporosis genes is the difficulty of obtaining bone tissue samples from large numbers of individuals. In this study, we tested the applicability of using peripheral blood mononuclear cell (PBMC)-derived transcriptional profiles as a surrogate to cortical bone transcriptional profiles to address questions of skeletal genetics. We used a well-established and genetically well-characterized nonhuman primate model for human bone maintenance and turnover. We determined that a high degree of overlap exists in gene expression of cortical bone and PBMCs and that genes in both the osteoporosis-associated RANK Osteoclast and Estrogen Receptor Signaling pathways are highly expressed in PBMCs. Genes within the Wnt Signaling pathway, also implicated in osteoporosis pathobiology, are expressed in PBMCs, albeit to a lesser extent. These results are the first in an effort to comprehensively characterize the relationship between the PBMC transcriptome and bone M-bM-^@M-^S knowledge that is essential for maximizing the use of PBMCs to identify genes and signaling pathways relevant to osteoporosis pathogenesis. It is also a first step in identifying genes that correlate in a predictable manner between PBMCs and cortical bone from healthy and osteoporotic individuals, potentially allowing us to identify genes that could be used to diagnose osteoporosis prior to detectible bone loss and with easily obtained PBMCs. Total RNA was isolated from peripheral blood mononuclear cells and cortical bone of a nonhuman primate model (Papio hamadryas ssp.) of bone maintenance and turnover. Both samples were taken from the same animal. Tissue from 15 animals was used for the study.

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Quantitative Proteomics Revealed the Changes of Pharmacodynamic Network of Bugu Shengsui Decoction Promoting Osteoblasts Proliferation

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