The multiple functions and mechanisms of osteopontin

İçer, Mehmet Arif; Karadağ, Makbule Gezmen

doi:10.1016/j.clinbiochem.2018.07.003

Cited by 449 publications

(387 citation statements)

References 93 publications

Supporting

Mentioning

372

Contrasting

Unclassified

Order By: Relevance

“…SPP1 has been nominated as an AD CSF biomarker in previous studies [106][107][108][109] . SPP1 is known to be involved in tissue repair 110 , and promotes phagocytosis of amyloid-β and an anti-inflammatory microglial phenotype 111,112 . It is closely associated with the CD44 receptor 113 , which is highly expressed on the surface of activated astrocytes 114 .…”

Section: Discussionmentioning

confidence: 99%

A Consensus Proteomic Analysis of Alzheimer’s Disease Brain and Cerebrospinal Fluid Reveals Early Changes in Energy Metabolism Associated with Microglia and Astrocyte Activation

Johnson

Dammer

Duong

et al. 2019

Preprint

View full text Add to dashboard Cite

Our understanding of the biological changes in the brain associated with Alzheimer's disease (AD) pathology and cognitive impairment remains incomplete. To increase our understanding of these changes, we analyzed dorsolateral prefrontal cortex of control, asymptomatic AD, and AD brains from four different centers by label-free quantitative mass spectrometry and weighted protein co-expression analysis to obtain a consensus protein co-expression network of AD brain.This network consisted of 13 protein co-expression modules. Six of these modules correlated with amyloid-β plaque burden, tau neurofibrillary tangle burden, cognitive function, and clinical functional status, and were altered in asymptomatic AD, AD, or in both disease states. These modules reflected synaptic, mitochondrial, sugar metabolism, extracellular matrix, cytoskeletal, and RNA binding/splicing biological functions. The identified protein network modules were preserved in a community-based cohort analyzed by a different quantitative mass spectrometry approach. They were also preserved in temporal lobe and precuneus brain regions. Some of the modules were influenced by aging, and showed changes in other neurodegenerative diseases such as frontotemporal dementia and corticobasal degeneration. The module most strongly associated with AD pathology and cognitive impairment was the sugar metabolism module, which was enriched in AD genetic risk factors and correlated with APOE genetic risk. This module was also highly enriched in microglia and astrocyte protein markers associated with an antiinflammatory state, suggesting that the biological functions it represents serve a protective role in AD. Proteins from this module were increased in cerebrospinal fluid from asymptomatic AD and AD cases, highlighting their potential as biomarkers of the altered brain network. In this study of >2000 brains and nearly 400 cerebrospinal fluid samples by quantitative proteomics, we identify proteins and biological processes in AD brain that may serve as therapeutic targets and fluid biomarkers for the disease. IntroductionAlzheimer's disease (AD) is a leading cause of death worldwide, with increasing prevalence as global life expectancy increases 1 . Although AD is currently defined on the basis of amyloid-β plaque and tau neurofibrillary tangle deposition within the neocortex 2 , the biochemical and cellular changes in the brain that characterize the disease beyond amyloid-β and tau deposition remain incompletely understood. The genetic architecture of late-onset AD has been extensively studied, and the results of these studies implicate multiple biological pathways that contribute to development of the disease, including immune function, endocytic vesicle trafficking, and lipid homeostasis, among others 3-5 . In addition to genetic studies, transcriptomic studies on postmortem AD brain tissue have identified changes in mRNA co-expression that correlate with disease traits and cognitive decline 6,7 . However, given that mRNA levels correlate only modestly to protein le...

show abstract

Section: Discussionmentioning

confidence: 99%

A Consensus Proteomic Analysis of Alzheimer’s Disease Brain and Cerebrospinal Fluid Reveals Early Changes in Energy Metabolism Associated with Microglia and Astrocyte Activation

Johnson

Dammer

Duong

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Even before microglia were formally identified, the presence of fat-laden cells had been reported and suggested to be a part of (49) the normal developing CNS (50)(51)(52), and to participate in either cell death processes (53) or myelin formation (54)(55)(56). Early after the initial description of microglial cells, neuroanatomists began to track and map microglia in the CNS.…”

Section: In Developmentmentioning

confidence: 99%

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

2020

View full text Add to dashboard Cite

Microglial heterogeneity has been the topic of much discussion in the scientific community. Elucidation of their plasticity and adaptability to disease states triggered early efforts to characterize microglial subsets. Over time, their phenotypes, and later on their homeostatic signature, were revealed, through the use of increasingly advanced transcriptomic techniques. Recently, an increasing number of these "microglial signatures" have been reported in various homeostatic and disease contexts. Remarkably, many of these states show similar overlapping microglial gene expression patterns, both in homeostasis and in disease or injury. In this review, we integrate information from these studies, and we propose a unique subset, for which we introduce a core signature, based on our own research and reports from the literature. We describe that this subset is found in development and in normal aging as well as in diverse diseases. We discuss the functions of this subset as well as how it is induced.

show abstract

“…[17][18][19] Recent studies conducted by our group and others have demonstrated the role of OPN and/or OC as structural molecules in bone matrix linking the organic and inorganic matrices and contributing to structural integrity of bone. 24,25 In bone, OPN is produced by osteoblasts during premineralization at the late stages of osteoblastic maturation. 24,25 In bone, OPN is produced by osteoblasts during premineralization at the late stages of osteoblastic maturation.…”

Section: Introductionmentioning

confidence: 99%

Synergistic effect of extracellularly supplemented osteopontin and osteocalcin on stem cell proliferation, osteogenic differentiation, and angiogenic properties

Carvalho

Cabral

Silva

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

A high demand for functional bone grafts is being observed worldwide, especially due to the increased life expectancy. Osteoinductive components should be incorporated into functional bone grafts, accelerating cell recruitment, cell proliferation, angiogenesis, and new bone formation at a defect site. Noncollagenous bone matrix proteins, especially osteopontin (OPN) and osteocalcin (OC), have been reported to regulate some physiological process, such as cell migration and bone mineralization. However, the effects of OPN and OC on cell proliferation, osteogenic differentiation, mineralization, and angiogenesis are still undefined. Therefore, we assessed the exogenous effect of OPN and OC supplementation on human bone marrow mesenchymal stem/stromal cells (hBM MSC) proliferation and osteogenic differentiation. OPN dose‐dependently increased the proliferation of hBM MSC, as well as improved the angiogenic properties of human umbilical vein endothelial cells (HUVEC) by increasing the capillary‐like tube formation in vitro. On the other hand, OC enhanced the differentiation of hBM MSC into osteoblasts and demonstrated an increase in extracellular calcium levels and alkaline phosphatase activity, as well as higher messenger RNA levels of mature osteogenic markers osteopontin and osteocalcin. In vivo assessment of OC/OPN‐enhanced scaffolds in a critical‐sized defect rabbit long‐bone model revealed no infection, while new bone was being formed. Taken together, these results suggest that OC and OPN stimulate bone regeneration by inducing stem cell proliferation, osteogenesis and by enhancing angiogenic properties. The synergistic effect of OC and OPN observed in this study can be applied as an attractive strategy for bone regeneration therapeutics by targeting different vital cellular processes.

show abstract

The multiple functions and mechanisms of osteopontin

Cited by 449 publications

References 93 publications

A Consensus Proteomic Analysis of Alzheimer’s Disease Brain and Cerebrospinal Fluid Reveals Early Changes in Energy Metabolism Associated with Microglia and Astrocyte Activation

A Consensus Proteomic Analysis of Alzheimer’s Disease Brain and Cerebrospinal Fluid Reveals Early Changes in Energy Metabolism Associated with Microglia and Astrocyte Activation

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

Synergistic effect of extracellularly supplemented osteopontin and osteocalcin on stem cell proliferation, osteogenic differentiation, and angiogenic properties

Contact Info

Product

Resources

About