자료유형  

 학위논문

Control Number  

0015493922

International Standard Book Number  

9781687965127

Dewey Decimal Classification Number  

617.6

Main Entry-Personal Name  

Clark, Daniel R.

Publication, Distribution, etc. (Imprint  

[Sl] : University of California, San Francisco, 2019

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2019

Physical Description  

103 p

General Note  

Source: Dissertations Abstracts International, Volume: 81-04, Section: B.

General Note  

Advisor: Marcucio, Ralph.

Dissertation Note  

Thesis (Ph.D.)--University of California, San Francisco, 2019.

Restrictions on Access Note  

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

Restrictions on Access Note  

This item must not be added to any third party search indexes.

Summary, Etc.  

요약Aging is characterized by physiologic changes leading to a predisposition to a myriad of age-related diseases. Accompanying these age-related diseases is a process of systemic inflammatory dysregulation known as inflamm-aging. This body of work focuses on fracture healing and periodontal disease, as both involve dysregulation of inflammation within bone and both demonstrate increased complications or prevalence with age. We chose to investigate the macrophage and its contribution to age-related pathologies affecting bone. Macrophages are important regulators of inflammation during fracture healing and periodontal disease. An improved understanding of the age-related changes to macrophages will advance our understanding of the biology of aging and lead to enhanced healthcare for the aging population. Mouse models of fracture healing and periodontal disease using young and old mice were employed in this work. Macrophages from young and old mice were characterized via RNA-seq. Macrophage were depleted pharmacologically during disease or fracture healing to elucidate the contribution of macrophages within the given models. The results demonstrated that macrophages from old mice present an aged-macrophage phenotype with increased pro-inflammatory and M1 gene expression. By eliminating the influence of the aged macrophage phenotype via macrophage depletion, periodontal disease severity was significantly reduced and fracture healing was significantly improved. Further, we have demonstrated that TREM2 expression on macrophages is decreased with age which drove increased inflammatory cytokine expression and poorer fracture healing outcomes. Taken together, the aged-related changes that occur to the macrophage are likely involved in numerous disease pathologies, and this work presents potential therapeutic targets to address the macrophage-driven inflammatory dysregulation in the elderly population.

Subject Added Entry-Topical Term  

Immunology

Subject Added Entry-Topical Term  

Aging

Subject Added Entry-Topical Term  

Dentistry

Added Entry-Corporate Name  

University of California, San Francisco Oral and Craniofacial Sciences

Host Item Entry  

Dissertations Abstracts International. 81-04B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:568813