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Resolving Macrophages Block Osteolys...

Viniegra Urbina, Ana Laura.

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Resolving Macrophages Block Osteolysis Through Anabolic Actions on Bone Cells.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Resolving Macrophages Block Osteolysis Through Anabolic Actions on Bone Cells./
Author:	Viniegra Urbina, Ana Laura.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
Description:	115 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-06, Section: B.
Contained By:	Dissertations Abstracts International80-06B.
Subject:	Biomedical engineering. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10933366
ISBN:	9780438683464

Resolving Macrophages Block Osteolysis Through Anabolic Actions on Bone Cells.
Viniegra Urbina, Ana Laura.

Resolving Macrophages Block Osteolysis Through Anabolic Actions on Bone Cells. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 115 p.

Source: Dissertations Abstracts International, Volume: 80-06, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2018.

This item must not be sold to any third party vendors.

Progression of inflammatory osteolytic diseases, including rheumatoid arthritis and periodontitis, is characterized by increased production of pro-inflammatory mediators and matrix degrading enzymes by macrophages, and increased osteoclastic activity. Phenotypic changes in macrophages are central to the healing process in virtually all tissues. In the present study, we assessed the timing of macrophage phenotypic changes and the impact of anti-inflammatory pro-resolving activation during inflammatory osteolysis and healing, using a murine model of periodontitis. Pro-inflammatory macrophage activation and TNF-α overproduction within three weeks after induction of periodontitis was associated with progressing bone loss. Pro-resolving activation within one week of stimulus removal and markers of resolving macrophages, IL-10, TGF-β and CD206 correlated strongly with bone levels. In vivo macrophage depletion with clodronate liposomes prevented bone resorption but impaired regeneration. Induction of resolving macrophages with rosiglitazone, a PPAR-γ agonist, led to reduced bone resorption during inflammatory stimulation and increased bone formation during healing. In vitro assessment of primary bone marrow-derived macrophages activated with either IFN-γ and LPS (pro-inflammatory activation) or IL-4 (pro-resolving activation) showed that IL-4-activated cells have enhanced resolving functions (production of anti-inflammatory cytokines, migration and phagocytosis of aged neutrophils), and exert direct anabolic actions on bone cells. Cystatin C secreted by resolving but not inflammatory macrophages explained, in part, the macrophage actions on osteoblasts and osteoclasts. This study supports the concept that therapeutic induction of pro-resolving functions in macrophages can re-couple bone resorption and formation in inflammatory osteolytic diseases.

ISBN: 9780438683464Subjects--Topical Terms:

535387
Biomedical engineering.

Resolving Macrophages Block Osteolysis Through Anabolic Actions on Bone Cells.
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520 $a Progression of inflammatory osteolytic diseases, including rheumatoid arthritis and periodontitis, is characterized by increased production of pro-inflammatory mediators and matrix degrading enzymes by macrophages, and increased osteoclastic activity. Phenotypic changes in macrophages are central to the healing process in virtually all tissues. In the present study, we assessed the timing of macrophage phenotypic changes and the impact of anti-inflammatory pro-resolving activation during inflammatory osteolysis and healing, using a murine model of periodontitis. Pro-inflammatory macrophage activation and TNF-α overproduction within three weeks after induction of periodontitis was associated with progressing bone loss. Pro-resolving activation within one week of stimulus removal and markers of resolving macrophages, IL-10, TGF-β and CD206 correlated strongly with bone levels. In vivo macrophage depletion with clodronate liposomes prevented bone resorption but impaired regeneration. Induction of resolving macrophages with rosiglitazone, a PPAR-γ agonist, led to reduced bone resorption during inflammatory stimulation and increased bone formation during healing. In vitro assessment of primary bone marrow-derived macrophages activated with either IFN-γ and LPS (pro-inflammatory activation) or IL-4 (pro-resolving activation) showed that IL-4-activated cells have enhanced resolving functions (production of anti-inflammatory cytokines, migration and phagocytosis of aged neutrophils), and exert direct anabolic actions on bone cells. Cystatin C secreted by resolving but not inflammatory macrophages explained, in part, the macrophage actions on osteoblasts and osteoclasts. This study supports the concept that therapeutic induction of pro-resolving functions in macrophages can re-couple bone resorption and formation in inflammatory osteolytic diseases.
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