All these functions make the approximately 206 bones of the human body an organ that is essential to our daily existence. Moreover, bone stores crucial nutrients, minerals, and lipids and produces blood cells that nourish the body and play a vital role in protecting the body against infection. Foster BL(1), Ao M(2), Salmon CR(3), Chavez MB(4), Kolli TN(4), Tran AB(2), Chu EY(2), Kantovitz KR(5), Yadav M(6), Narisawa S(6), Millán JL(6), Nociti FH Jr(3), Somerman MJ(2). In spite of this, it is currently unknown whether OC and OPN alter bone morphology and consequently affect bone fracture resistance. Extracellular matrix proteins such as osteopontin (OPN) could play a role in mediation of the mechanical stress signal to osteoblasts. Osteopontin (OPN) is a phosphorylated acidic glycoprotein that has been implicated in a number of physiological and pathological events, including maintenance or reconfiguration of tissue integrity during inflammatory processes. Gene structure and chromosomal location positive regulation of bone resorption Source: GO_Central "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium." Osteopontin takes a role in bone tissue destruction by two basic mechanisms. OPN can be secreted, or it can be retained intracellularly where it is associated with the CD44 complex (51). Altered wound healing in mice lacking a functional osteopontin gene (spp1). The primary source of OPN in dystrophic muscle is immune cells, although myogenic cells also express it (4; and unpublished data). OPN is also a critical molecule in the crosstalk between biliary epithelial cells, progenitor cells, and HSCs. Osteopontin (OPN) is a multifunctional protein, and although highly expressed in bone, it is also expressed by various cell types including macrophages, endothelial cells, smooth muscle cells and epithelial cells. OPN has been evaluated in various experimental models of kidney injury, and multiple studies have reported the detection of OPN mRNA in regenerating proximal tubules in renal ischemia models.103,104 The elevated levels of OPN are sustained for 7 days after the injury. OPN can activate macrophages via induction of IL-12 synthesis and suppression of IL-10 expression [80]. We use cookies to help provide and enhance our service and tailor content and ads. Osteopontin (OPN) is an acidic phosphoprotein that is highly expressed in DMD biopsies and mdx muscles (4). Thus, this SNP in OPN appears to be the first genetic modifier of the DMD phenotype and lends strong support for OPN as a therapeutic target. Background Osteopontin (OPN) has been implicated in bone remodeling by activating the resorption process. The number of hematopoietic stem and progenitor cells (HSPC) in an osteopontin-deficient BMM was increased, suggesting that osteopontin negatively regulates HSC (Stier et al., 2005). Véronique Orian-Rousseau, Jonathan Sleeman, in Advances in Cancer Research, 2014. There is preliminary evidence in humans that OPN also promotes progression of DMD. Secretion of osteopontin by macrophages and its accumulation at tissue surfaces during wound healing in mineralized tissues: A potential requirement for macrophage adhesion and phagocytosis. In mice, OPN is positively correlated with airway remodeling and stimulates collagen deposition in cell cultures. , Thomas P.D. OPN has recently been shown to modulate CD44-dependent activation of Met in hepatocellular carcinoma (HCC). It has been suggested that tumor cells produce OPN that could protect tumor cells themselves against the attack by macrophages by suppressing their production of nitric oxide (NO), which can kill tumor cells. OPN plays a critical role in the maintenance of bone, especially as a molecule involved in the response of bones to external stress. Osteopontin is a ligand for the alpha4beta1 integrin. The role of OPN in bone and in the immune system. In the post-MI setting, OPN co-localizes with macrophages infiltrating the infarct area, indicating OPN originates from or cross talks with macrophages. Osteopontin (OPN) is a TH1 cytokine implicated as a potential regulator of allergic responses. Gaudet P. , Livstone M.S. Further investigations are required to elucidate the molecular mechanisms of OPN action in mediating responses to inflammation, mechanical stress, angiogenesis, and accelerated bone resorption. Osteopontin as a target for cancer therapy. Osteopontin (OPN) is a potent regulator of hematopoietic stem cells [1]. Here we show that osteopontin (OPN), an extracellular matrix molecule secreted by osteoblasts, can function to anchor leukemic blasts in anatomic locations supporting tumor dormancy. It was originally discovered to regulate bone ⦠Smooth muscle cells also express osteopontin and respond to mechanical stress. Expression of osteopontin at sites of bone erosion in a murine experimental arthritis model of collageninduced arthritis: possible involvement of osteopontin in bone destruction in arthritis. We aimed to study the relationship between OPN, bone mineral density (BMD), bone turnover markers, vitamin D, and osteoporotic vertebral fractures in postmenopausal women. Consistent with its role in other systems, OPN proved to be an immunomodulator, that when targeted, resulted in reduced neutrophils and NKT cells and reductions in TGF-β. Overexpression of OPN in HSCs resulted in increased collagen-I production through engagement of integrin αvβ3 and activation of the PI3k/Akt pathway [170]. A cleaved fragment of osteopontin accumulates in bone marrow, and may contribute to the actions of osteopontin by binding to α9β1 and α4β1 integrins on HSCs and hematopoietic progenitors.75, Joseph V. Bonventre M.D., Ph.D., Venkata Sabbisetti Ph.D., in Chronic Kidney Disease, Dialysis, and Transplantation (Third Edition), 2010. Osteopontin (OPN) regulates the immune response at multiple levels. OPN may also contribute to airway remodeling through the regulation of cellular interactions with ECM as well as the expression of MMP. Taking into account the reciprocal relationship between OPN and MMP9, it is feasible that pharmacological inhibition of both could be synergistic and therapeutically beneficial. As such, it is required for stress-induced bone remodeling and certain types of cell-mediated immunity. OPN, a multifunctional protein, is considered crucial for bone remodeling, biomineralization, and periodontal remodeling during mechanical tension and stress (orthodontic tooth movement). Secreted OPN binds to integrins and CD44 as well as to several extracellular matrix molecules including fibronectin and collagen (52,53). Using a cDNA microarray, OPN was identified as one of the genes upregulated in activated HSCs, where incubation with recombinant OPN induced proliferative and migratory effects. LSF controls expression of OPN, which in turn activates Met through interacting with CD44 (Yoo et al., 2011). Semantic Scholar is a free, AI-powered research tool for scientific literature, based at the Allen Institute for AI. Osteopontin inhibits induction of nitric oxide synthase gene expression by inflammatory mediators in mouse kidney epithelial cells. Among them, we showed that osteopontin (OPN) plays an important role in response to mechanical loading in rats with an experimental system for tooth movement. OPN also has a large number of consensus sequence sites for post-translational phosphorylation of Ser residues to form phosphoserine, providing additional negative charge. Osteonectin also increases the production and activity of matrix metalloproteinases, a function important to invading cancer cells within bone. Osteopontin (OPN) is a multifunctional protein mainly associated with bone metabolism and remodeling. Although this review is written ⦠In addition, ovalbumin sensitization and challenge of osteopontin-deficient mice results in an accentuated allergen-specific-IgE response. Umeshita-Sasai M, Mima T, Nomura S, Kobayashi H, Yamaguchi N, Nishioka K Umeshita-Sasai. The maintenance of bone, especially as a means to cope with environmental:....It is widely expressed in osteoclasts and is also involved in other homeostatic defense mechanism the..., providing additional negative charge 170 ] cancer research, 2014 krause, in Principles of bone remodeling alveolar. ) has been implicated in the pathogenesis of a variety of disease states, such Asp. Enhanced collagen-I synthesis by HSCs [ 171 ] recent accumulation of a body of new data has opened new! 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