TY - JOUR
T1 - The Role of Osteopontin in Microglia Biology
T2 - Current Concepts and Future Perspectives
AU - Rosmus, Dennis Dominik
AU - Lange, Clemens
AU - Ludwig, Franziska
AU - Ajami, Bahareh
AU - Wieghofer, Peter
N1 - Funding Information:
Research reported in this paper was supported in part by a grant from the U.S. Department of Defense through the U.S. Fish and Wildlife Service (Agreement 601814J251). The authors thank Bruce Rosenlund, U.S. Fish and Wildlife Service, Project Leader, CO FWAO; Tom Warren, Director, Directorate of Environmental Compliance and Management at Ft. Carson; Dr. Brian Mihlbachler, Natural Resources Manager, U.S. Air Force Academy; Floyd Hatch, Natural and Cultural Resources Coordinator, Buckley Air Force Base; Cathy Pesenti, Environmental Management Flight, F. E. Warren Air Force Base; and Amy Thorn-burg, U.S. Fish and Wildlife Service, Rocky Flats National Wildlife Refuge site for their continued support and assistance in the noxious weed biological control implementation program.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/4
Y1 - 2022/4
N2 - The innate immune landscape of the central nervous system (CNS), including the brain and the retina, consists of different myeloid cell populations with distinct tasks to fulfill. Whereas the CNS borders harbor extraparenchymal CNS-associated macrophages whose main duty is to build up a defense against invading pathogens and other damaging factors from the periphery, the resident immune cells of the CNS parenchyma and the retina, microglia, are highly dynamic cells with a plethora of functions during homeostasis and disease. Therefore, microglia are constantly sensing their environment and closely interacting with surrounding cells, which is in part mediated by soluble factors. One of these factors is Osteopontin (OPN), a multifunctional protein that is produced by different cell types in the CNS, including microglia, and is upregulated in neurodegenerative and neuroinflammatory conditions. In this review, we discuss the current literature about the interaction between microglia and OPN in homeostasis and several disease entities, including multiple sclerosis (MS), Alzheimer’s and cerebrovascular diseases (AD, CVD), amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD) and diabetic retinopathy (DR), in the context of the molecular pathways involved in OPN signaling shaping the function of microglia. As nearly all CNS diseases are characterized by pathological alterations in microglial cells, accompanied by the disturbance of the homeostatic microglia phenotype, the emergence of disease-associated microglia (DAM) states and their interplay with factors shaping the DAM-signature, such as OPN, is of great interest for therapeutical interventions in the future.
AB - The innate immune landscape of the central nervous system (CNS), including the brain and the retina, consists of different myeloid cell populations with distinct tasks to fulfill. Whereas the CNS borders harbor extraparenchymal CNS-associated macrophages whose main duty is to build up a defense against invading pathogens and other damaging factors from the periphery, the resident immune cells of the CNS parenchyma and the retina, microglia, are highly dynamic cells with a plethora of functions during homeostasis and disease. Therefore, microglia are constantly sensing their environment and closely interacting with surrounding cells, which is in part mediated by soluble factors. One of these factors is Osteopontin (OPN), a multifunctional protein that is produced by different cell types in the CNS, including microglia, and is upregulated in neurodegenerative and neuroinflammatory conditions. In this review, we discuss the current literature about the interaction between microglia and OPN in homeostasis and several disease entities, including multiple sclerosis (MS), Alzheimer’s and cerebrovascular diseases (AD, CVD), amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD) and diabetic retinopathy (DR), in the context of the molecular pathways involved in OPN signaling shaping the function of microglia. As nearly all CNS diseases are characterized by pathological alterations in microglial cells, accompanied by the disturbance of the homeostatic microglia phenotype, the emergence of disease-associated microglia (DAM) states and their interplay with factors shaping the DAM-signature, such as OPN, is of great interest for therapeutical interventions in the future.
KW - AMD
KW - Alzheimer’s disease
KW - CNS
KW - Inflammation
KW - Macrophages
KW - Microglia
KW - Multiple sclerosis
KW - Neurodegeneration
KW - Osteopontin
KW - Retina
KW - SPP1
UR - http://www.scopus.com/inward/record.url?scp=85128512504&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85128512504&partnerID=8YFLogxK
U2 - 10.3390/biomedicines10040840
DO - 10.3390/biomedicines10040840
M3 - Article
AN - SCOPUS:85128512504
SN - 2227-9059
VL - 10
JO - Biomedicines
JF - Biomedicines
IS - 4
M1 - 840
ER -