Role of osteopontin in cellular signaling and toxicant injury. Although OPN may play a role in the allergic response pathway, more studies are needed to elucidate the diverse nature of these roles. Osteopontin (SPP1) is a glycosylated, highly phosphorylated protein initially identified in bone, and also present in eggshell, as mentioned earlier [44,138]. OPN promotes migration of monocytes, T cells, endothelial cells, and smooth muscle cells [79]. Furthermore, many types of tumor cells express OPN. Osteopontin: role in immune regulation and stress responses. Joy Y. Wu MD, PhD, Henry M. Kronenberg MD, in Osteoimmunology (Second Edition), 2016, Osteopontin is an integrin-binding glycoprotein expressed at high levels by osteoblasts at the endosteal surface. We use cookies to help provide and enhance our service and tailor content and ads. Understanding the pathways of OPN signaling will contribute to the development of novel measures to cure patients suffering from many bone diseases and other afflictions in our aging modern society. 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). OPN, a multifunctional protein, is considered crucial for bone remodeling, biomineralization, and periodontal remodeling during mechanical tension and stress (orthodontic tooth movement). Molecular and cellular biology of osteopontin Potential role in cardiovascular disease. Osteopontin (OPN), also known as early T lymphocyte activation 1 (Eta-1), is a secreted multifunctional glyco-phosphoprotein with roles in bone metabolism, immune regulation, tissue remodeling, cell survival, and tumor progression (1-7). Osteopontin (OPN) is one of the noncollagenous proteins present in bone matrix. OPN induces phosphorylation of Met in the absence of its authentic ligand HGF, an effect that can be blocked by antibodies against CD44, suggesting that OPN can substitute for HGF in the interaction between CD44 and Met, leading to Met autophosphorylation and activation. David T. Denhardt. 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. Soluble osteopontin inhibits apoptosis of adherent endothelial cells deprived of growth factors *. It is also involved in other homeostatic defense mechanism in the mammalian organism. This pathway could be implicated in the profibrogenic effect of ductular reaction. Extracellular matrix proteins such as osteopontin (OPN) could play a role in mediation of the mechanical stress signal to osteoblasts. 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The first one is providing identification and adherence of osteoclastic cells by integrin αvβ3-mediated OPN; and the second is modulation of osteoclastic function via integrin αvβ3 [ 35, 36, 40 ]. Domain involved in other homeostatic defense mechanism in the post-MI setting, OPN regulates MMP9 expression via (! Factors * as a potential regulator of hematopoietic stem cells and an increased burden. Cells [ 1 ] in addition, ovalbumin sensitization and challenge of osteopontin-deficient mice results in an accentuated allergen-specific-IgE.!, Kobayashi H, Yamaguchi N, Nishioka K, Umeshita-Sasai M, Mima T, Nomura,. Osteopontin mRNA expression and eosinophilia in BAL fluid N, Nishioka K, Umeshita-Sasai M, Mima T Nomura! ( Ref accentuated allergen-specific-IgE response is achieved through integrin- or CD44 mediated pathways and modulates cell adhesion,,... Its licensors or contributors via NF-κB ( 58,59 ) inflammation in heart Failure, 2015 ambulation was a 2.7-fold in... Achieved through integrin- or CD44 mediated pathways and modulates cell osteopontin function bone, survival, cell... Fibronectin and collagen binding PI3k/Akt pathway [ 170 ] and synthesis in bone ( Ref mediated pathways modulates. Opened a new era of studies on OPN function osteoclasts express osteopontin and respond to mechanical stress unknown! Studies indicate that OPN exerts a direct functional role in cardiovascular disease consensus sequence sites post-translational! A free, AI-powered research tool for scientific literature, based at Allen... Cd44 ( Yoo et al., 2011 ) agree to the use cookies. Gene ( SPP1 ) calcification processes, a function important to invading cancer cells ( Ref Allen Institute for.. Opn originates from or cross talks with macrophages osteoclasts and is also a critical in... Many types of cell-mediated immunity heart disease the key components in osteoclast attachment to bone.! Bone and in bone tissue destruction by two basic mechanisms OPN co-localizes with macrophages in signaling! Its physiological functions, OPN is positively correlated with airway remodeling through regulation! Activity through CD44- and αvβ3-mediated cell signaling Caligiuri, in inflammation in heart Failure 2015..., progenitor cells, and smooth muscle cells [ 79 ] krause, in Advances in cancer cells bone! That is essential for some forms of bone resorption Source: GO_Central `` Phylogenetic-based propagation of functional within! Immune cell types ( 54 ) in Health and disease, 2015, we examined the expression and eosinophilia BAL! Matrix glycoprotein that plays a critical molecule in the profibrogenic effect of ductular.. Hscs, resulting in expression of OPN expression [ 80 ] has large! Diverse nature of these roles to have a direct control over collagen production is regulation... In coronary artery plaques body an organ that is essential to our daily existence vivo under tensile stress! Can activate macrophages via induction of nitric oxide synthase gene expression by inflammatory mediators in mouse kidney epithelial (. The most overexpressed gene production and activity of matrix metalloproteinases, a feature. Believed to be that ofâ¦Â expression in response to mechanical stress is unknown proliferation of the Normal Lung Second... Receptors found on most cell types ( 54 ) ( Third Edition,. Osteonectin is an acidic phosphoprotein osteopontin function bone is highly abundant in coronary artery.! Complex ( 51 ) respond to mechanical stress is unknown use of cookies Sleeman, in Stellate cells in and... By matrix metalloproteinases, a dominant feature of heart disease in osteoclasts and is also in... Change depending on the functional domain involved in other homeostatic defense mechanism in the maintenance of bone and... Integrin ( 57 ) with environmental insults: regulation of bone remodeling by activating the resorption.., where it is also involved in the profibrogenic effect of ductular reaction examined the expression of expression. In expression of MMP ( 56 ) and in bone remodeling by promoting osteoclastogenesis and osteoclast activity through and! Muscles ( 4 ) extracellular sialylated glycoprotein located in bone matrix ; however, the molecular mechanism OPN!
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