Roles of fibrinolytic factors in the alterations in bone marrow hematopoietic stem/progenitor cells during bone repair

Abstract In bone tissues, metabolic turnover through bone resorption by osteoclasts and bone formation by osteoblasts, termed bone remodeling, is strictly controlled and maintains homeostasis. Fibrinolytic factors are expressed in osteoclasts and osteoblasts, and are involved in bone remodeling thro...

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Main Authors: Kiyotaka Okada, Minoru Nishioka, Hiroshi Kaji
Format: Article
Language:English
Published: BMC 2020-09-01
Series:Inflammation and Regeneration
Subjects:
Online Access:http://link.springer.com/article/10.1186/s41232-020-00128-5
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author Kiyotaka Okada
Minoru Nishioka
Hiroshi Kaji
author_facet Kiyotaka Okada
Minoru Nishioka
Hiroshi Kaji
author_sort Kiyotaka Okada
collection DOAJ
description Abstract In bone tissues, metabolic turnover through bone resorption by osteoclasts and bone formation by osteoblasts, termed bone remodeling, is strictly controlled and maintains homeostasis. Fibrinolytic factors are expressed in osteoclasts and osteoblasts, and are involved in bone remodeling through bone resorption and formation. The repair/regeneration process after bone injury is divided into the acute inflammatory, repair, and remodeling stages. Osteoblasts, osteoclasts, chondrocytes, and macrophages involved in the bone repair process originate from hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stem cells (MSCs) in the bone marrow. Therefore, stem cells in the bone marrow may be strongly influenced by bone injury. The urokinase-type PA (u-PA)/plasminogen (Plg) system functions in macrophage accumulation/phagocytosis through chemokines in the acute inflammatory stage, and Plg increases blood vessel-related growth factor expression, being involved in vascularization in mice. Plasminogen activator inhivitor-1 (PAI-1) causes bone loss and delayed bone repair through the inhibition of osteoblast differentiation in a drug-induced diabetes model in mice. Plg is considered to induce transforming growth factor-β (TGF-β) production in macrophages in the bone repair process, TGF-β release from the extracellular matrix through the activation of matrix metalloproteinase-9 (MMP-9), and stromal cell-derived factor-1 (SDF-1) expression in endosteal preosteoblasts, leading to the induction of bone marrow HSPCs in mice. Based on the above, establishment of a fibrinolytic factor-targeting method efficiently promoting bone repair/regeneration and fracture healing, and development of a new osteoporosis treatment method and diagnostic marker are awaited.
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spelling doaj.art-e5a60c1aa95a4779b7039d9a76a2c0dc2022-12-21T20:33:44ZengBMCInflammation and Regeneration1880-81902020-09-014011710.1186/s41232-020-00128-5Roles of fibrinolytic factors in the alterations in bone marrow hematopoietic stem/progenitor cells during bone repairKiyotaka Okada0Minoru Nishioka1Hiroshi Kaji2Department of Arts and Science, Kindai University Faculty of MedicineDepartment of Physiology and Regenerative Medicine, Kindai University Faculty of MedicineDepartment of Physiology and Regenerative Medicine, Kindai University Faculty of MedicineAbstract In bone tissues, metabolic turnover through bone resorption by osteoclasts and bone formation by osteoblasts, termed bone remodeling, is strictly controlled and maintains homeostasis. Fibrinolytic factors are expressed in osteoclasts and osteoblasts, and are involved in bone remodeling through bone resorption and formation. The repair/regeneration process after bone injury is divided into the acute inflammatory, repair, and remodeling stages. Osteoblasts, osteoclasts, chondrocytes, and macrophages involved in the bone repair process originate from hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stem cells (MSCs) in the bone marrow. Therefore, stem cells in the bone marrow may be strongly influenced by bone injury. The urokinase-type PA (u-PA)/plasminogen (Plg) system functions in macrophage accumulation/phagocytosis through chemokines in the acute inflammatory stage, and Plg increases blood vessel-related growth factor expression, being involved in vascularization in mice. Plasminogen activator inhivitor-1 (PAI-1) causes bone loss and delayed bone repair through the inhibition of osteoblast differentiation in a drug-induced diabetes model in mice. Plg is considered to induce transforming growth factor-β (TGF-β) production in macrophages in the bone repair process, TGF-β release from the extracellular matrix through the activation of matrix metalloproteinase-9 (MMP-9), and stromal cell-derived factor-1 (SDF-1) expression in endosteal preosteoblasts, leading to the induction of bone marrow HSPCs in mice. Based on the above, establishment of a fibrinolytic factor-targeting method efficiently promoting bone repair/regeneration and fracture healing, and development of a new osteoporosis treatment method and diagnostic marker are awaited.http://link.springer.com/article/10.1186/s41232-020-00128-5Bone regenerationFibrinolytic factorHematopoietic stem/progenitor cellsStromal cell-derived factor-1Transforming growth factor-β
spellingShingle Kiyotaka Okada
Minoru Nishioka
Hiroshi Kaji
Roles of fibrinolytic factors in the alterations in bone marrow hematopoietic stem/progenitor cells during bone repair
Inflammation and Regeneration
Bone regeneration
Fibrinolytic factor
Hematopoietic stem/progenitor cells
Stromal cell-derived factor-1
Transforming growth factor-β
title Roles of fibrinolytic factors in the alterations in bone marrow hematopoietic stem/progenitor cells during bone repair
title_full Roles of fibrinolytic factors in the alterations in bone marrow hematopoietic stem/progenitor cells during bone repair
title_fullStr Roles of fibrinolytic factors in the alterations in bone marrow hematopoietic stem/progenitor cells during bone repair
title_full_unstemmed Roles of fibrinolytic factors in the alterations in bone marrow hematopoietic stem/progenitor cells during bone repair
title_short Roles of fibrinolytic factors in the alterations in bone marrow hematopoietic stem/progenitor cells during bone repair
title_sort roles of fibrinolytic factors in the alterations in bone marrow hematopoietic stem progenitor cells during bone repair
topic Bone regeneration
Fibrinolytic factor
Hematopoietic stem/progenitor cells
Stromal cell-derived factor-1
Transforming growth factor-β
url http://link.springer.com/article/10.1186/s41232-020-00128-5
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AT minorunishioka rolesoffibrinolyticfactorsinthealterationsinbonemarrowhematopoieticstemprogenitorcellsduringbonerepair
AT hiroshikaji rolesoffibrinolyticfactorsinthealterationsinbonemarrowhematopoieticstemprogenitorcellsduringbonerepair