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      Identification of osteoporosis markers through bioinformatic functional analysis of serum proteome

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          Abstract

          Osteoporosis is a severe chronic skeletal disorder that increases the risks of disability and mortality; however, the mechanism of this disease and the protein markers for prognosis of osteoporosis have not been well characterized. This study aims to characterize the imbalanced serum proteostasis, the disturbed pathways, and potential serum markers in osteoporosis by using a set of bioinformatic analyses. In the present study, the large-scale proteomics datasets (PXD006464) were adopted from the Proteome Xchange database and processed with MaxQuant. The differentially expressed serum proteins were identified. The biological process and molecular function were analyzed. The protein–protein interactions and subnetwork modules were constructed. The signaling pathways were enriched. We identified 209 upregulated and 230 downregulated serum proteins. The bioinformatic analyses revealed a highly overlapped functional protein classification and the gene ontology terms between the upregulated and downregulated protein groups. Protein–protein interactions and pathway analyses showed a high enrichment in protein synthesis, inflammation, and immune response in the upregulated proteins, and cell adhesion and cytoskeleton regulation in the downregulated proteins. Our findings greatly expand the current view of the roles of serum proteins in osteoporosis and shed light on the understanding of its underlying mechanisms and the discovery of serum proteins as potential markers for the prognosis of osteoporosis.

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          TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease

          Transforming growth factor-beta (TGF-β) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-βs and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-β/BMP ligands, receptors, and Smads) and the non-canonical-Smad-independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis. Both the Smad and p38 MAPK signaling pathways converge at transcription factors, for example, Runx2 to promote osteoblast differentiation and chondrocyte differentiation from mesenchymal precursor cells. TGF-β and BMP signaling is controlled by multiple factors, including the ubiquitin–proteasome system, epigenetic factors, and microRNA. Dysregulated TGF-β and BMP signaling result in a number of bone disorders in humans. Knockout or mutation of TGF-β and BMP signaling-related genes in mice leads to bone abnormalities of varying severity, which enable a better understanding of TGF-β/BMP signaling in bone and the signaling networks underlying osteoblast differentiation and bone formation. There is also crosstalk between TGF-β/BMP signaling and several critical cytokines’ signaling pathways (for example, Wnt, Hedgehog, Notch, PTHrP, and FGF) to coordinate osteogenesis, skeletal development, and bone homeostasis. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in osteoblast differentiation, chondrocyte differentiation, skeletal development, cartilage formation, bone formation, bone homeostasis, and related human bone diseases caused by the disruption of TGF-β/BMP signaling.
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            Pathways of antigen processing.

            T cell recognition of antigen-presenting cells depends on their expression of a spectrum of peptides bound to major histocompatibility complex class I (MHC-I) and class II (MHC-II) molecules. Conversion of antigens from pathogens or transformed cells into MHC-I- and MHC-II-bound peptides is critical for mounting protective T cell responses, and similar processing of self proteins is necessary to establish and maintain tolerance. Cells use a variety of mechanisms to acquire protein antigens, from translation in the cytosol to variations on the theme of endocytosis, and to degrade them once acquired. In this review, we highlight the aspects of MHC-I and MHC-II biosynthesis and assembly that have evolved to intersect these pathways and sample the peptides that are produced.
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              Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination.

              Phosphatidylinositide 3 kinases (PI3Ks) and their downstream mediators AKT and mammalian target of rapamycin (mTOR) constitute the core components of the PI3K/AKT/mTOR signalling cascade, regulating cell proliferation, survival and metabolism. Although these functions are well-defined in the context of tumorigenesis, recent studies - in particular those using pluripotent stem cells - have highlighted the importance of this pathway to development and cellular differentiation. Here, we review the recent in vitro and in vivo evidence for the role PI3K/AKT/mTOR signalling plays in the control of pluripotency and differentiation, with a particular focus on the molecular mechanisms underlying these functions.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0025-7974
                1536-5964
                25 September 2020
                25 September 2020
                : 99
                : 39
                : e22172
                Affiliations
                [a ]Institute of Translational Medicine, Medical College, Yangzhou University
                [b ]Jiangsu Key Laboratory of Experimental and Translational Non-coding RNA Research, Yangzhou, Jiangsu, PR China
                [c ]School of Graduate Studies, Rutgers, The State University of New Jersey, Newark, NJ
                [d ]No. 5 Region, The First Affiliated Hospital of Guangzhou University of Chinese Medicine
                [e ]Department of Joint Diseases, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine
                [f ]Traumatology and Orthopedics Institute of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
                Author notes
                []Correspondence: Ziqi Li, the Third Affiliated Hospital, Traumatology and Orthopedics Institute of Guangzhou, University of Chinese Medicine, China (e-mail: ionsev0214@ 123456126.com ).
                Article
                MD-D-18-06386 22172
                10.1097/MD.0000000000022172
                7523818
                32991410
                1d46d1b9-3737-46aa-a6c8-9daf9544e77f
                Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                : 6 September 2018
                : 12 July 2020
                : 12 August 2020
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81603641
                Award Recipient : Peng Chen
                Funded by: Guangdong Science and Technology Department
                Award ID: No.2017A020213030
                Award Recipient : Ziqi Li
                Funded by: Natural Science Foundation of Jiangsu Province
                Award ID: BK20180927
                Award Recipient : Mengying Lv
                Funded by: Zhejiang Traditional Chinese Medicine Administration (CN)
                Award ID: YB201850
                Award Recipient : Mengying Lv
                Categories
                4100
                Research Article
                Observational Study
                Custom metadata
                TRUE

                bioinformatics,differentially expressed proteins,osteoporosis,protein markers,serum proteome

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