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Zhao Z, Du Y, Yan K, Zhang L, Guo Q. Exercise and osteoimmunology in bone remodeling. FASEB J 2024; 38:e23554. [PMID: 38588175 DOI: 10.1096/fj.202301508rrr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 02/20/2024] [Accepted: 02/28/2024] [Indexed: 04/10/2024]
Abstract
Bones can form the scaffolding of the body, support the organism, coordinate somatic movements, and control mineral homeostasis and hematopoiesis. The immune system plays immune supervisory, defensive, and regulatory roles in the organism, which mainly consists of immune organs (spleen, bone marrow, tonsils, lymph nodes, etc.), immune cells (granulocytes, platelets, lymphocytes, etc.), and immune molecules (immune factors, interferons, interleukins, tumor necrosis factors, etc.). Bone and the immune system have long been considered two distinct fields of study, and the bone marrow, as a shared microenvironment between the bone and the immune system, closely links the two. Osteoimmunology organically combines bone and the immune system, elucidates the role of the immune system in bone, and creatively emphasizes its interdisciplinary characteristics and the function of immune cells and factors in maintaining bone homeostasis, providing new perspectives for skeletal-related field research. In recent years, bone immunology has gradually become a hot spot in the study of bone-related diseases. As a new branch of immunology, bone immunology emphasizes that the immune system can directly or indirectly affect bones through the RANKL/RANK/OPG signaling pathway, IL family, TNF-α, TGF-β, and IFN-γ. These effects are of great significance for understanding inflammatory bone loss caused by various autoimmune or infectious diseases. In addition, as an external environment that plays an important role in immunity and bone, this study pays attention to the role of exercise-mediated bone immunity in bone reconstruction.
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Affiliation(s)
- Zhonghan Zhao
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China
| | - Yuxiang Du
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China
| | - Kai Yan
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China
| | - Lingli Zhang
- College of Athletic Performance, Shanghai University of Sport, Shanghai, China
| | - Qiang Guo
- Department of Orthopaedics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
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Nong J, Lu G, Huang Y, Liu J, Chen L, Pan H, Xiong B. Identification of cuproptosis-related subtypes, characterization of immune microenvironment infiltration, and development of a prognosis model for osteoarthritis. Front Immunol 2023; 14:1178794. [PMID: 37809099 PMCID: PMC10551149 DOI: 10.3389/fimmu.2023.1178794] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 08/07/2023] [Indexed: 10/10/2023] Open
Abstract
Background Osteoarthritis (OA) is a prevalent chronic joint disease with an obscure underlying molecular signature. Cuproptosis plays a crucial role in various biological processes. However, the association between cuproptosis-mediated immune infifiltration and OA progression remains unexplored. Therefore, this study elucidates the pathological process and potential mechanisms underlying cuproptosis in OA by constructing a columnar line graph model and performing consensus clustering analysis. Methods Gene expression profifile datasets GSE12021, GSE32317, GSE55235, and GSE55457 of OA were obtained from the comprehensive gene expression database. Cuproptosis signature genes were screened by random forest (RF) and support vector machine (SVM). A nomogram was developed based on cuproptosis signature genes. A consensus clustering was used to distinguish OA patients into different cuproptosis patterns. To quantify the cuproptosis pattern, a principal component analysis was developed to generate the cuproptosis score for each sample. Single-sample gene set enrichment analysis (ssGSEA) was used to provide the abundance of immune cells in each sample and the relationship between these significant cuproptosis signature genes and immune cells.To quantify the cuproptosis pattern, a principal component analysis technique was developed to generate the cuproptosis score for each sample. Cuproptosis-related genes were extracted and subjected to differential expression analysis to construct a disease prediction model and confifirmed by RT-qPCR. Results Seven cuproptosis signature genes were screened (DBT, LIPT1, GLS, PDHB, FDX1, DLAT, and PDHA1) to predict the risk of OA disease. A column line graph model was developed based on these seven cuproptosis signature genes, which may assist patients based on decision curve analysis. A consensus clustering method was used to distinguish patients with disorder into two cuproptosis patterns (clusters A and B). To quantify the cuproptosis pattern, a principal component analysis technique was developed to generate the cuproptosis score for each sample. Furthermore, the OA characteristics of patients in cluster A were associated with the inflflammatory factors IL-1b, IL-17, IL-21, and IL-22, suggesting that the cuproptosis signature genes play a vital role in the development of OA. Discussion In this study, a risk prediction model based on cuproptosis signature genes was established for the fifirst time, and accurately predicted OA risk. In addition, patients with OA were classifified into two cuproptosis molecule subtypes (clusters A and B); cluster A was highly associated with Th17 immune responses, with higher IL-1b, IL-17, and IL-21 IL-22 expression levels, while cluster B had a higher correlation with cuproptosis. Our analysis will help facilitate future research related cuproptosis-associated OA immunotherapy. However, the specifific mechanisms remain to be elucidated.
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Affiliation(s)
- Jiao Nong
- Teaching Department, First Affiliated Hospital of the Guangxi University of Chinese Medicine, Nanning, China
| | - Guanyu Lu
- Postgraduate Schools, Guangxi University of Chinese Medicine, Nanning, China
| | - Yue Huang
- Postgraduate Schools, Guangxi University of Chinese Medicine, Nanning, China
| | - Jinfu Liu
- Postgraduate Schools, Guangxi University of Chinese Medicine, Nanning, China
| | - Lihua Chen
- Postgraduate Schools, Guangxi University of Chinese Medicine, Nanning, China
| | - Haida Pan
- Postgraduate Schools, Guangxi University of Chinese Medicine, Nanning, China
| | - Bo Xiong
- Department of Knee Arthropathy and Sports Injuries, Yulin Orthopedic Hospital of Integrated Traditional Chinese and Western Medicine, Yulin, China
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Vlashi R, Zhang X, Wu M, Chen G. Wnt signaling: essential roles in osteoblast differentiation, bone metabolism and therapeutic implications for bone and skeletal disorders. Genes Dis 2022. [DOI: 10.1016/j.gendis.2022.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022] Open
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Martínez-Gil N, Ugartondo N, Grinberg D, Balcells S. Wnt Pathway Extracellular Components and Their Essential Roles in Bone Homeostasis. Genes (Basel) 2022; 13:genes13010138. [PMID: 35052478 PMCID: PMC8775112 DOI: 10.3390/genes13010138] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/10/2022] [Accepted: 01/11/2022] [Indexed: 12/11/2022] Open
Abstract
The Wnt pathway is involved in several processes essential for bone development and homeostasis. For proper functioning, the Wnt pathway is tightly regulated by numerous extracellular elements that act by both activating and inhibiting the pathway at different moments. This review aims to describe, summarize and update the findings regarding the extracellular modulators of the Wnt pathway, including co-receptors, ligands and inhibitors, in relation to bone homeostasis, with an emphasis on the animal models generated, the diseases associated with each gene and the bone processes in which each member is involved. The precise knowledge of all these elements will help us to identify possible targets that can be used as a therapeutic target for the treatment of bone diseases such as osteoporosis.
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Krstić J, Mojsilović S, Mojsilović SS, Santibanez JF. Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation. World J Stem Cells 2021; 13:1696-1713. [PMID: 34909118 PMCID: PMC8641017 DOI: 10.4252/wjsc.v13.i11.1696] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 05/14/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Bone regeneration is a tightly regulated process that ensures proper repair and functionality after injury. The delicate balance between bone formation and resorption is governed by cytokines and signaling molecules released during the inflammatory response. Interleukin (IL)-17A, produced in the early phase of inflammation, influences the fate of osteoprogenitors. Due to their inherent capacity to differentiate into osteoblasts, mesenchymal stem/stromal cells (MSCs) contribute to bone healing and regeneration. This review presents an overview of IL-17A signaling and the leading cellular and molecular mechanisms by which it regulates the osteogenic differentiation of MSCs. The main findings demonstrating IL-17A’s influence on osteoblastogenesis are described. To this end, divergent information exists about the capacity of IL-17A to regulate MSCs’ osteogenic fate, depending on the tissue context and target cell type, along with contradictory findings in the same cell types. Therefore, we summarize the data showing both the pro-osteogenic and anti-osteogenic roles of IL-17, which may help in the understanding of IL-17A function in bone repair and regeneration.
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Affiliation(s)
- Jelena Krstić
- Gottfried Schatz Research Center, Medical University of Graz, Graz 8010, Austria
| | - Slavko Mojsilović
- Group for Hematology and Stem Cells, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Belgrade 11129, Serbia
| | - Sonja S Mojsilović
- Group for Immunology, Institute for Medical Research, National Institute of Republic of Serbia, Belgrade 11129, Serbia
| | - Juan F Santibanez
- Group for Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Belgrade 11000, Serbia
- Centro Integrativo de Biología y Química Aplicada, Universidad Bernardo O’Higgins, Chile 8370993, Chile
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Rossi M, Rana I, Buonuomo PS, Battafarano G, De Martino V, D'Agostini M, Porzio O, Cipriani C, Minisola S, De Vito R, Vecchio D, Gonfiantini MV, Jenkner A, Bartuli A, Del Fattore A. Stimulation of Treg Cells to Inhibit Osteoclastogenesis in Gorham-Stout Disease. Front Cell Dev Biol 2021; 9:706596. [PMID: 34513837 PMCID: PMC8430039 DOI: 10.3389/fcell.2021.706596] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 08/10/2021] [Indexed: 11/18/2022] Open
Abstract
Gorham-Stout disease (GSD) is a very rare syndrome displaying excessive bone erosion and vascular lesion. Due to the rarity of the disease and to the limited studies, its etiopathogenesis is not entirely known. The involvement of immune system in the progressive osteolysis was recently suggested. Indeed, extensive reciprocal interactions between the immune and skeletal systems have been demonstrated. This study aimed to evaluate alterations of immune cells in GSD. An increase of CD8+ cells and reduction of CD4+ and CD4+CD25+CD127low cells was revealed in patients. Interestingly, patients’ regulatory T cells maintain the ability to respond to extracellular stimuli and to regulate osteoclastogenesis; GSD cells proliferate under aCD3/CD28 signal reaching similar levels to those observed in control culture and exert their immunomodulatory activity on effector T cells. GSD Treg cells preserved their inhibitory effects on the osteoclastogenesis. These results suggest that stimulation of Treg cells could open the way for the identification and testing of new therapeutic approaches for patients affected by GSD.
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Affiliation(s)
- Michela Rossi
- Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Ippolita Rana
- Rare Diseases and Medical Genetic Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Paola Sabrina Buonuomo
- Rare Diseases and Medical Genetic Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Giulia Battafarano
- Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Viviana De Martino
- Department of Clinical, Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University, Rome, Italy
| | - Matteo D'Agostini
- Clinical Laboratory, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Ottavia Porzio
- Clinical Laboratory, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.,Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Cristiana Cipriani
- Department of Clinical, Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University, Rome, Italy
| | - Salvatore Minisola
- Department of Clinical, Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University, Rome, Italy
| | - Rita De Vito
- Department of Histopathology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Davide Vecchio
- Rare Diseases and Medical Genetic Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | | | - Alessandro Jenkner
- Division of Immunology and Infectious Diseases, Department of Pediatrics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Andrea Bartuli
- Rare Diseases and Medical Genetic Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Andrea Del Fattore
- Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
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Sun M, Chen Z, Wu X, Yu Y, Wang L, Lu A, Zhang G, Li F. The Roles of Sclerostin in Immune System and the Applications of Aptamers in Immune-Related Research. Front Immunol 2021; 12:602330. [PMID: 33717084 PMCID: PMC7946814 DOI: 10.3389/fimmu.2021.602330] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 01/14/2021] [Indexed: 12/19/2022] Open
Abstract
Wnt signaling is one of the fundamental pathways that play a major role in almost every aspect of biological systems. In addition to the well-known influence of Wnt signaling on bone formation, its essential role in the immune system also attracted increasing attention. Sclerostin, a confirmed Wnt antagonist, is also proven to modulate the development and differentiation of normal immune cells, particularly B cells. Aptamers, single-stranded (ss) oligonucleotides, are capable of specifically binding to a variety of target molecules by virtue of their unique three-dimensional structures. With in-depth study of those functional nucleic acids, they have been gradually applied to diagnostic and therapeutic area in immune diseases due to their various advantages over antibodies. In this review, we focus on several issues including the roles of Wnt signaling and Wnt antagonist sclerostin in the immune system. For the sake of understanding, current examples of aptamers applications for the immune diseases are also discussed. At the end of this review, we propose our ideas for the future research directions.
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Affiliation(s)
- Meiheng Sun
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China
| | - Zihao Chen
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Xiaoqiu Wu
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China
| | - Yuanyuan Yu
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China
| | - Luyao Wang
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China
| | - Aiping Lu
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China.,Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.,Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai, China
| | - Ge Zhang
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China
| | - Fangfei Li
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China
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8
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Zhu L, Hua F, Ding W, Ding K, Zhang Y, Xu C. The correlation between the Th17/Treg cell balance and bone health. IMMUNITY & AGEING 2020; 17:30. [PMID: 33072163 PMCID: PMC7557094 DOI: 10.1186/s12979-020-00202-z] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 10/06/2020] [Indexed: 02/08/2023]
Abstract
With the ageing of the world population, osteoporosis has become a problem affecting quality of life. According to the traditional view, the causes of osteoporosis mainly include endocrine disorders, metabolic disorders and mechanical factors. However, in recent years, the immune system and immune factors have been shown to play important roles in the occurrence and development of osteoporosis. Among these components, regulatory T (Treg) cells and T helper 17 (Th17) cells are crucial for maintaining bone homeostasis, especially osteoclast differentiation. Treg cells and Th17 cells originate from the same precursor cells, and their differentiation requires involvement of the TGF-β regulated signalling pathway. Treg cells and Th17 cells have opposite functions. Treg cells inhibit the differentiation of osteoclasts in vivo and in vitro, while Th17 cells promote the differentiation of osteoclasts. Therefore, understanding the balance between Treg cells and Th17 cells is anticipated to provide a new idea for the development of novel treatments for osteoporosis.
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Affiliation(s)
- Lei Zhu
- The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Jiangsu, 213003 China
| | - Fei Hua
- The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Jiangsu, 213003 China
| | - Wenge Ding
- The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Jiangsu, 213003 China
| | - Kai Ding
- The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Jiangsu, 213003 China
| | - Yige Zhang
- The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Jiangsu, 213003 China
| | - Chenyang Xu
- The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Jiangsu, 213003 China
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Comprehensive Analysis of Differentially Expressed Circular RNAs in Patients with Senile Osteoporotic Vertebral Compression Fracture. BIOMED RESEARCH INTERNATIONAL 2020; 2020:4951251. [PMID: 33083467 PMCID: PMC7556071 DOI: 10.1155/2020/4951251] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 08/18/2020] [Accepted: 08/24/2020] [Indexed: 12/21/2022]
Abstract
Aim Circular RNAs (circRNAs) have been found to contribute to the regulation of many diseases and are abundantly expressed in various organisms. The present study is aimed at systematically characterizing the circRNA expression profiles in patients with senile osteoporotic vertebral compression fracture (OVCF) and predicting the potential functions of the regulatory networks correlated with these differentially expressed circRNAs. Methods The circRNA expression profile in patients with senile OVCF was explored by using RNA sequencing. The prediction of the enriched signaling pathways and circRNA-miRNA networks was conducted by bioinformatics analysis. Real-time quantitative PCR was used to validate the selected differentially expressed circRNAs from 20 patients with senile OVCF relative to 20 matched healthy controls. Results A total of 884 differentially expressed circRNAs were identified, of which 554 were upregulated and 330 were downregulated. The top 15 signaling pathways associated with these differentially expressed circRNAs were predicted. The result of qRT-PCR of the selected circRNAs was consistent with RNA sequencing. Conclusions CircRNAs are differentially expressed in patients with senile OVCF, which might contribute to the pathophysiological mechanism of senile osteoporosis.
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Zhao J, Jing J, Zhao W, Li X, Hou L, Zheng C, Kong Q, Li W, Yao X, Chang L, Li H, Mu L, Wang G, Wang J. Osteopontin exacerbates the progression of experimental autoimmune myasthenia gravis by affecting the differentiation of T cell subsets. Int Immunopharmacol 2020; 82:106335. [PMID: 32109680 DOI: 10.1016/j.intimp.2020.106335] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 02/13/2020] [Accepted: 02/19/2020] [Indexed: 11/23/2022]
Abstract
Osteopontin (OPN) is a multifunctional extracellular matrix phosphoprotein that has a specific and complicated structure, and contributes to numerous physiological and pathological activities. The mechanism of OPN in many diseases has been confirmed; however, the role of OPN in myasthenia gravis (MG) remains unclear. In this study, we recombined rat OPN protein in vitro, and assessed how OPN affects the development of autoimmunity using an experimental autoimmune myasthenia gravis (EAMG) rat model. The results showed that the concentration of OPN in serum was up-regulated. Both mRNA and protein levels in splenocytes increased in the EAMG model. OPN treatment in vitro strongly promoted the differentiation of Th1 cells, and inhibited the differentiation of Treg cells. Intraperitoneal injection of OPN revealed the early incidence of EAMG, and more serious disease. This effect was accompanied by an increased percentage of Th1 cells. In conclusion, OPN likely exacerbates the pathogenesis of EAMG by promoting the differentiation of Th1 cells and inhibiting the differentiation of Treg cells.
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Affiliation(s)
- Jiarui Zhao
- Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China
| | - Jia Jing
- Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China
| | - Wei Zhao
- Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China
| | - Xinrong Li
- Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China
| | - Lixuan Hou
- Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China
| | - Chunfeng Zheng
- The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar City, Heilongjiang 161000, China
| | - Qingfei Kong
- Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China
| | - Wenjin Li
- Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China
| | - Xiuhua Yao
- Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, Tianjin 300350, China
| | - Lulu Chang
- Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China
| | - Hulun Li
- Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China; Ministry of Education Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China, Harbin Medical University, Harbin, Heilongjiang 150086, China
| | - Lili Mu
- Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China; Ministry of Education Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China, Harbin Medical University, Harbin, Heilongjiang 150086, China.
| | - Guangyou Wang
- Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China.
| | - Jinghua Wang
- Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China.
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Chicana B, Donham C, Millan AJ, Manilay JO. Wnt Antagonists in Hematopoietic and Immune Cell Fate: Implications for Osteoporosis Therapies. Curr Osteoporos Rep 2019; 17:49-58. [PMID: 30835038 PMCID: PMC6715281 DOI: 10.1007/s11914-019-00503-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW We reviewed the current literature on the roles of the Wnt antagonists sclerostin (Sost) and sclerostin-containing domain protein 1 (Sostdc1) on bone homeostasis, the relationship of the hypoxia-inducible factor (Hif) and von Hippel-Lindau (Vhl) pathways on Sost expression, and how changes in bone induced by depletion of Sost, Sostdc1, and Vhl affect hematopoietic cells. RECENT FINDINGS B cell development is adversely affected in Sost-knockout mice and is more severely affected in Vhl-knockout mice. Inflammation in the Sost-/- bone microenvironment could alter hematopoietic stem cell behavior. Sostdc1-/- mice display defects in natural killer cell development and cytotoxicity. Depletion of Sost and Sostdc1 have effects on immune cell function that warrant investigation in patients receiving Wnt antagonist-depleting therapies for treatment of bone diseases. Additional clinical applications for manipulation of Wnt antagonists include cancer immunotherapies, stem cell transplantation, and directed differentiation to immune lineages.
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Affiliation(s)
- Betsabel Chicana
- Quantitative and Systems Biology Graduate Program, University of California, Merced, CA, USA
| | - Cristine Donham
- Quantitative and Systems Biology Graduate Program, University of California, Merced, CA, USA
| | - Alberto J Millan
- Quantitative and Systems Biology Graduate Program, University of California, Merced, CA, USA
| | - Jennifer O Manilay
- Quantitative and Systems Biology Graduate Program, University of California, Merced, CA, USA.
- Department of Molecular and Cell Biology, School of Natural Sciences, University of California, 5200 North Lake Road, Merced, CA, 95343, USA.
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