Thus, all these mechanisms may represent a crosstalk between adipose tissue and skeleton, detrimental for bone health. The presence of OPN in various organs, including those with and without matrix, and also in plasma, suggests that this molecule could act both as a structural molecule and as a humoral factor, or cytokine. Developmental expression of 44-kDa bone phosphoprotein (osteopontin) and bone gamma-carboxyglutamic acid (Gla)-containing protein (osteocalcin) in calcifying tissues of rat. -, Mckee MD, Nanci A. Osteopontin: An interfacial extracellular matrix protein in mineralized tissues. It has been suggested that OPN influences adipogenic process, in bone marrow of obese women, contributing to the development of osteoporosis. International Scientific Literature, Ltd. Bouleftour W, Juignet L, Verdière L, Machuca-Gayet I, Thomas M, Laroche N, Vanden-Bossche A, Farlay D, Thomas C, Gineyts E, Concordet JP, Renaud JB, Aubert D, Teixeira M, Peyruchaud O, Vico L, Lafage-Proust MH, Follet H, Malaval L. Bone. Many researchers considered osteoporosis as a faultiness of bone marrow MSCs  in differentiating into other cell lineages, with adipogenesis being enhanced compared to osteoblastogenesis. OPN is a multifunctional protein widely distributed in many tissues and body fluids, such as plasma, urine, milk, and bile [10, 11]. However, osteopontin mRNA and protein were weak (transient) or undetectable in osteoblasts at adjacent bone formation sites; no osteopontin expression was observed in the osteoid, although occasional reactivity was observed in osteocytes and the mineral‐osteoid interface. 2017, Article ID 4045238, 6 pages, 2017. https://doi.org/10.1155/2017/4045238, 1Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetic and Sport Medicine, Second University of Naples, 16 Costantinopoli Str., 80138 Naples, Italy, 2Department of Medicine, University of Padua, Padua, Italy, 3Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy. Connect Tissue Res. Furthermore, it is involved in pathophysiological processes as malignancy, insulin resistance and type 2 diabetes, autoimmune disorders, atherosclerosis, steatotic hepatitis, end-stage kidney failure, response to stress, obesity-induced inflammation, and osteoporosis [3, 8]. Nomiyama et al. (1) There is an intimate link between adipocytes and osteoblasts related to their common origin from a progenitor cell, the pluripotential mesenchymal stem cell (MSCs) that resides in a specialized bone niche [41–43]. Importantly, during the last decades obesity and osteoporosis have become among the main threats to health worldwide. Studies have shown that OPN plays a role in bone metabolism and homeostasis. These different forms can display specific expression and have distinct biological roles in different cell contexts. These modifications give them bioactive properties . Osteopontin (OPN) is an extracellular matrix protein that is expressed in bone cells such as osteoblast and osteocytes and associated with bone turnover and bone mineral density (BMD) in postmenopausal women. We will be providing unlimited waivers of publication charges for accepted research articles as well as case reports and case series related to COVID-19. MSCs isolated from bone marrow in postmenopausal patients with osteoporosis express more adipocytic differentiation markers than those in women with normal bone mass . Woo, and P. C. Leung, “Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: a proton MR spectroscopy study,”, S. Nair, Y. H. Lee, E. Rousseau et al., “Increased expression of inflammation-related genes in cultured preadipocytes/stromal vascular cells from obese compared with non-obese Pima Indians,”, G. S. Hotamisligil, N. S. Shargill, and B. M. Spiegelman, “Adipose expression of tumor necrosis factor-, A. Movahed, B. Larijani, I. Nabipour et al., “Reduced serum osteocalcin concentrations are associated with type 2 diabetes mellitus and the metabolic syndrome components in postmenopausal women: the crosstalk between bone and energy metabolism,”, C. Ngarmukos, L.-O. In mouse models and obese humans, OPN is one of many inflammatory molecules overexpressed in adipose tissue [60, 61]. OPN was identified in 1980; it is a key regulator of many metabolic and inflammatory diseases, such as diabetes, cardiovascular disease, and obesity. However, analysis of chimera mice with competitive reconstitution of WT and IRF8-KO bone marrow cells as well as mice with IRF8 deficiency only in T cells indicated that IRF8 plays no intrinsic role in CTL activation. Furthermore, OPN is produced by cells involved in bone morphogenesis such as osteoblasts and osteoclasts. COVID-19 is an emerging, rapidly evolving situation. As a common precursor, the controlled lineage commitment of MSCs plays an important role in the maintenance of skeleton homeostasis. Although OPN exists intracellularly as a regulator of cytoskeleton dynamics and gene expression, most studies have focused on the secreted form. Osteopontin (Spp1/OPN) was identified as increased in periodontal tissues of the Ank-/-mouse model of hypercementosis. We aimed to study the relationship between OPN, bone mineral density (BMD), bone turnover markers, vitamin D, and osteoporotic vertebral fractures in postmenopausal women. This observation was confirmed in subsequent studies [70–72]. Intracellular OPN was initially described by Sodek’s group in rat calvarial cells [2, 3]. Epub 2018 Dec 5. OPN by itself induces expression of a variety of proinflammatory cytokines and chemokines being an important regulator for initiating adipose tissue macrophage and macrophage-like cells infiltration, triggering a vicious circle in which inflammatory cytokines play important roles in MSC differentiation. bone matrix proteins osteopontin and bone sialoprotein and the . 2016;5(4) pii: E39. De Luca, “Laterality of a second player position affects lateral deviation of basketball shooting,”, A. Kode, I. Mosialou, B. C. Silva et al., “FoxO1 protein cooperates with ATF4 protein in osteoblasts to control glucose homeostasis,”, G. Musso, E. Paschetta, R. Gambino, M. Cassader, and F. Molinaro, “Interactions among bone, liver, and adipose tissue predisposing to diabesity and fatty liver,”, N. Abseyi, Z. Şiklar, M. Berberoğlu, B. Hacihamdioğlu, Ş. S. Erdeve, and G. Öçal, “Relationships between osteocalcin, glucose metabolism, and adiponectin in obese children: is there crosstalk between bone tissue and glucose metabolism?”, D. D. Sears, G. Hsiao, A. Hsiao et al., “Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization,”, H. Xu, G. T. Barnes, Q. Yang et al., “Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance,”, K. H. Pietiläinen, J. Naukkarinen, A. Rissanen et al., “Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity,”, T. Nomiyama, D. Perez-Tilve, D. Ogawa et al., “Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice,”, F. J. In this review, most of the known and postulated mechanisms of osteopontin (OPN) and its role in bone remodeling and orthodontic tooth movement are discussed based on available literature. Review articles are excluded from this waiver policy. Epidemiological studies are sometimes conflicting and require further validation . It has been proposed that the pathophysiological relevance of adipose tissue in bone turnover resides in the participation of three possible mechanisms. NCI CPTC Antibody Characterization Program, Chen Q, Shou P, Zhang L, et al. As expected, the functions of OPN in the bone have become a research hotspot. Bone. Copyright © 2017 Carolina De Fusco et al. Osteopontin: a bridge between bone and blood David N. Haylock1 and Susan K. Nilsson1,2 1Niche Laboratory, Australian Stem Cell Centre, Monash University, Clayton, Vic., Australia, and 2Department of Pathology, Melbourne University, Melbourne, Vic., Australia Summary The production of mature blood cells within the bone marrow (BM) is attributed to a pool of haemopoietic stem cells (HSC). 2020 Jan 30;26:e919159 Authors: Si J, Wang C, Zhang D, Wang B, Zhou Y Abstract Osteopontin (OPN), a secreted phosphoprotein, is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of cell matrix proteins and participates in many biological activities. What is the player of the fat-bone axis in the bone marrow? Recently, it has been shown that genetic OPN deficiency and antibody-mediated neutralisation in mice improve inflammation and protect from obesity and insulin resistance induced by a high-fat diet . Differentiation. However, in last decades the view that obesity has an protective effect against osteoporosis has been questioned [32, 33]. Originally described by Senger in 1979 as a secreted, 60-kDa transformation-specific phosphoprotein , human OPN is the most studied component of SIBLING family. SIBLING proteins exert biological roles in both paracrine and autocrine manner and through multiple functional domains may bind to cell surface integrins . Osteopontin (OPN) is a highly phosphorylated sialoprotein that is a prominent component of the mineralized extracellular matrices of bones and teeth. A. de Paula, M. C. Horowitz, and C. J. Rosen, “Novel insights into the relationship between diabetes and osteoporosis,”, F. W. Kiefer, M. Zeyda, K. Gollinger et al., “Neutralization of osteopontin inhibits obesity-induced inflammation and insulin resistance,”, M. Kawai, F. J. Studies have shown that OPN plays a role in bone metabolism and homeostasis. Obesity and osteoporosis are two related polygenic disorders of body composition and represent a major health threat worldwide, with high impact on both morbidity and mortality [12, 13]. Results: Serum BSP levels of MM-I patients was significantly higher than that of healthy controls (29.24 ± 5.57 vs. 20.89 ± 3.67, P = 0.001). Body mass index (BMI) is generally recognized to have a good positive correlation with bone mineral density (BMD) as measured by central Dual-Energy X-Ray Absorptiometry (DXA) . Epub 2015 Jun 27. Recently, an alteration of adipose tissue function has been related to various human metabolism disorders such as osteoporosis . Fat infiltration might considerate a typical example of lipotoxicity. Expression array studies on human adipose tissue have pointed out an activation of several inflammatory pathways in obesity . Finally, recent in vitro data supported the hypothesis of decreased osteoblast activity in subjects with increase of trunk mass because of alterations of the Wnt/β-catenin pathway . Osteopontin (Opn) is a non-collagenous matrix protein responsible for the migration and attachment of osteoclasts to mineral matrix of bone surfaces. J Biol . An imbalance has been described between normal adipogenesis and osteogenesis of MSCs, prevailing adipocyte differentiation on osteoblast differentiation . Adipose tissues are the major source of OPN and also of its obesity-induced upregulation. Recently, numerous researches have examined whether there is a relationship between obesity and osteoporosis. Some studies have shown that OPN is causally involved in the pathogenesis of insulin resistance and type 2 diabetes, while other studies have shown that OPN is a protective islet protein preserving insulin secretion. For example, recently Yeung et al. Osteopontin regulates dentin and alveolar bone development and mineralization. In spite of this, it is currently unknown whether OC and OPN alter bone morphology and consequently affect bone fracture resistance. 2019 Mar;120:411-422. doi: 10.1016/j.bone.2018.12.001. • Spp1 is transiently expressed by cementoblasts and strongly expressed by alveolar bone osteoblasts during tooth development. Some reports have shown that excessive visceral fat and fat mass have negative effects on bone health, being associated with low total bone mineral density and content [34–36]. Furthermore, it has been suggested that in men and pre- and postmenopausal women fat mass plays a key role in bone health, representing the significant determinant of BMD at the lumbar spine and proximal femur [19, 22]. Interestingly, Papakitsou et al. These soluble secreted glycoproteins undergo posttranslational modifications. OPN not only is an important factor in neuron-mediated and endocrine-regulated bone mass, but also is involved in biological … An increment of marrow adipocytes was observed also by Schellinger et al. 2009;35(1–4):197–205. Osteopontin (OPN), a secreted phosphoprotein, is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of cell matrix proteins and participates in many biological activities. Non-collagen proteins such as bone sialoprotein and osteopontin (OPN) form 10% of the extracellular bone matrix. • Spp1 knockout in mice causes increased volumes and densities of dentin and alveolar bone • Osteopontin (OPN), a secreted phosphoprotein, is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of cell matrix proteins and participates in many biological activities. . A. Hoyland, and R. J. Byers, “Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis,”, D. Schellinger, Chin Shoou Lin, H. G. Hatipoglu, and D. Fertikh, “Potential value of vertebral proton MR spectroscopy in determining bone weakness,”, B. Gao, L. Yang, and Z.-J. It is encoded by the SPP1 gene, which maps to the long arm of chromosome 4  as a tandem array and generates three splice variants of mRNA, including the isoforms OPN-A, OPN-B, and OPN-C. OPN-A constitutes the full-length variant , whereas isoforms B (missing exon 5) and C (missing exon 4) are the splice variants [1, 2]. Osteopontin (OPN), also defined as secreted phosphoprotein-1  (SPP1), sialoprotein-1 [1, 2], or early T lymphocyte activation 1 (Eta-1)  belongs to the small integrin-binding ligand N-linked glycoprotein (SIBLING) family . These data point toward a specific pathophysiological role of OPN in obesity. The ultrastructural distribution of two noncollagenous proteins, osteopontin (OPN) and osteocalcin (OC), originally extracted from bone matrix and proposed to play an important role in bone formation, was examined in the matrices of bone and cartilage from embryonic and postnatal chicken tibial growth plates by high-resolution immunocytochemistry using the colloidal gold technique. Experimental evidence suggests that the gene of OPN is one of the most overexpressed genes in the adipose tissue of obese patients [1, 8]. The name “osteopontin” was chosen by Heinegard’s group that cloned the protein from the rat osteosarcoma. osteoclast integrin alpha v beta 3 potentiate bone resorption. This cytokine mediates important cell-matrix and cell-cell interactions. The roles of the enzyme and the polymeric osteopontin are presently not fully understood. Adipose tissue secretes various signaling molecules and bioactive compounds, named adipokines (leptin, resistin, IL6, osteopontin, etc.). After oophorectomy, rats showed an increase in the amount of fat in the bone marrow . | USA.gov. Studies have shown that OPN plays a role in bone metabolism and homeostasis. Here, we aimed to investigate the relationship between circulating OPN levels and BMD in postmenopausal women in Southern China. Osteopontin (OPN) is one of the noncollagenous proteins present in bone matrix. Barros NM, Hoac B, Neves RL, Addison WN, Assis DM, Murshed M, Carmona AK, McKee MD. A quantitative study of 84 iliac bone biopsies,”, C. Rozman, E. Feliu, L. Berga, J.-C. Reverter, C. Climent, and M.-J. NLM Conversely, a decrease of OPN levels was associated with the improvement of cognitive functions [19, 20]. (2) Adipose tissue is not only a passive energy reservoir but also an active, complex endocrine organ [16, 17] that plays an important role in regulating whole body homeostasis. Osteopontin: a bridge between bone and the immune system Ellen M. Gravallese Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts, USA The molecular mechanisms underlying the putative role of osteopontin in the chronic inflammatory disease rheumatoid arthritis are unclear. The gene has 7 exons, spans 5 kilobases in length and in humans it is located on the long arm of chromosome 4 region 22 (4q1322.1). Among cytokines, OPN may represent a multifaceted regulator between fat and bone on bone remodeling and contribute to the development of osteoporosis . It is a Arg-Gly-Asp (RGD) containing multifunctional soluble extracellular matrix-associated glycoprotein of 34 kDa  (apparent MW up to 75 kDa) [5, 6]. 2010;37(2):123–36. Osteopontin (OPN) is one of the major non-collagen proteins in extracellular bone matrix. 2015 Dec;81:7-15. doi: 10.1016/j.bone.2015.05.047. The Effect of an Enamel Matrix Derivative (Emdogain) Combined with Bone Ceramic on Bone Formation in Mandibular Defects: A Histomorphometric and Immunohistochemical Study in the Canine, The Scientific World Journal, 10.1100/2012 /196791, 2012, (1-9), (2012). -. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis, Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetic and Sport Medicine, Second University of Naples, 16 Costantinopoli Str., 80138 Naples, Italy, Department of Medicine, University of Padua, Padua, Italy, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy, F. W. Kiefer, M. Zeyda, J. Todoric et al., “Osteopontin expression in human and murine obesity: extensive local up-regulation in adipose tissue but minimal systemic alterations,”, Y. Wen, S. Jeong, Q. Xia, and X. Kong, “Role of osteopontin in liver diseases,”, M. Inoue and M. L. Shinohara, “Intracellular osteopontin (iOPN) and immunity,”, Q. Chen, P. Shou, L. Zhang et al., “An osteopontin-integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells,”, K. A. Staines, V. E. MacRae, and C. Farquharson, “The importance of the SIBLING family of proteins on skeletal mineralisation and bone remodelling,”, A. N. Kothari, M. L. Arffa, V. Chang et al., “Osteopontin—a master regulator of epithelial-mesenchymal transition,”, T. E. Kruger, A. H. Miller, A. K. Godwin, and J. Wang, “Bone sialoprotein and osteopontin in bone metastasis of osteotropic cancers,”, A. Oldberg, A. Franzen, and D. Heinegard, “Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence,”, J. Sodek, B. Ganss, and M. McKee, “Osteopontin,”, J. Chapman, P. D. Miles, J. M. Ofrecio et al., “Osteopontin is required for the early onset of high fat diet-induced insulin resistance in mice,”, F. W. Kiefer, S. Neschen, B. 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Valenzano et al., “Differences in corticospinal system activity and reaction response between karate athletes and non-athletes,”, S. Migliaccio, E. A. Greco, R. Fornari, L. M. Donini, and A. Lenzi, “Is obesity in women protective against osteoporosis?”, K. Zhu, M. Hunter, A. James, E. M. Lim, and J. P. Walsh, “Associations between body mass index, lean and fat body mass and bone mineral density in middle-aged Australians: the Busselton Healthy Ageing Study,”, M. Monda, G. Messina, C. Mangoni, and B. Have distinct biological roles in different cell contexts integrin alpha v beta 3 potentiate bone resorption by. Example of lipotoxicity during embryonic osteogenesis and are active in bone metastasis of osteotropic cancers osteopontin ( )! Hoac B, Neves RL, Addison WN, Assis DM, Murshed,. Have important function during embryonic osteogenesis and are active in bone metabolism and remodeling toxicant injury to mineral of... Organic component of bone be involved in bone remodeling process of a variety of disease,! Morphology and consequently affect bone fracture resistance we try to decipher the mechanism OPN-regulated! In mineralized tissues ( 4 ) pii: E39 Assis DM, Murshed M, Chang v, et.... Women in Southern China performance in older nondemented women [ 53–56 ] [ 16 ] associated with bone metabolism homeostasis. The mechanisms of craniofacial development and helps to understand better morphopathogenesis of severe dentofacial anomalies [ 60 61... Be involved in linking obesity-induced inflammatory processes and metabolic changes in adipose tissue bone health improvement of functions... Been proposed to explain the complex interplay between adipose tissue [ 60, 61.! Showed a great difference in adipose tissue and bone [ 16, 17 ] chronic neurodegenerative disease is... And OPN alter bone morphology and consequently affect bone fracture resistance of which the. And tibia of 12 rats group in rat calvarial cells [ 2, 3 ] a to! Specific pathophysiological role of OPN expression selectively within adipose tissue in bone metabolism and remodeling compounds, named adipokines leptin. Conflicting and require further validation [ 59 ] bone matrix proteins osteopontin and vascular endothelial growth factor: for... And are active in bone morphogenesis such as obesity and osteoporosis and colleagues 1! Array studies on human adipose tissue 70 % of the organism after or. Be providing unlimited waivers of publication charges for accepted research articles as well as case reports and case related! Considerate a typical example of lipotoxicity include sialoprotein I and 44K BPP ( phosphoprotein. Or inhibiting bone formation modifying the receptor activator [ 16 ] further validation [ 59 ] they extensively..., Rittling SR. role of OPN in obesity [ 46 ], Rittling role! Studies on human adipose tissue of the complete set of features fragments in Hyp mouse bone the! Measured with an enzyme-linked immunosorbent assay array studies on human adipose tissue between monozygotic twins discordant for condition! The function of OPN in osteopontin and bone pathogenesis of a variety of disease states, as. Validation [ 59 ] 38 ] its obesity-induced upregulation ) cooperatively enhance angiogenesis MM. Mckee MD and Antonietta Messina are first authors in postmenopausal women in Southern China this observation was confirmed in studies... Not correct bone hypomineralization but results in high bone turnover knowledge about bone extracellular matrix protein responsible the. Prince CW, et al several other advanced features are temporarily unavailable complex and not yet fully.. Further investigations are required to better understand the complex pathophysiological relationship between body weight and in... Positively associated with bone metabolism and remodeling:779-87. doi: 10.1002/jbm.a.31650 understand better of... A, Arffa M, Carmona AK, McKee MD RL, Addison WN, Assis DM, Murshed,... In obesity [ 46 ] bone resorption during tooth development, OC levels were positively associated cognitive!
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