Understanding Osteoarthritis as a Biological and Biomechanical Disease
Hui Mingalone, Carrie.
2018
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Abstract: Osteoarthritis (OA), a degenerative joint condition characterized by
progressive loss of articular cartilage and other joint tissue changes, is the most common
cause of disability in the United States. OA is a disease with multifactorial etiology
resulting in heterogeneous disease onset and progression, but the same ending of joint
degeneration. Current treatment options are focused ... read moreon managing OA symptoms, specifically
pain, but do not treat the underlying cause of disease. A major hurdle for better therapies
is the lack of understanding of OA disease initiation and progression, especially at early
stages of prior to clinical symptoms. This thesis present two independent projects seeking
to understand the roles of biochemical and biomechanical factors in OA development. In the
field of OA research, biochemical changes are understood to occur in early OA. There is an
increase in cartilage metabolism and a decrease in catabolism, which contributes to
cartilage loss and other joint tissue changes. Inflammation is thought to be a major driver
of these biochemical changes underlying structural changes. One aspect of this thesis
focuses on understanding inflammatory dynamics driven by master transcriptional regulator
NFκB and how it may be related to cartilage structural changes. Results from this study
showed that NFκB driven inflammation, visualized via bioluminescence imaging, peaks early
in a post-traumatic OA (PTOA) mouse model and that structural modifications, visualized as
collagen fiber thickness and orientation changes through second harmonic generation
imaging, also occur in early OA across different cartilage layers. The second project of
this thesis is focused on understanding the interplay between biochemical (specifically
glucose) and biomechanical factors in OA progression utilizing a novel ex vivo joint
culturing system, the Joint-in-Motion 1 (JM1) device. In this study, whole mouse knee
joints were cultured in media solutions with variable glucose and osmolarity with dynamic
input. While joint spatial orientation, cell numbers, and extracellular matrix collagen II
was preserved, proteoglycan was lost only in joints cultured in high glucose with dynamic
movement. This study revealed the synergistic effects of biomechanical and biomechanical
factors in OA development and highlights a possible role for glucose in priming the joint
for damage via biomechanical stress
Thesis (Ph.D.)--Tufts University, 2018.
Submitted to the Dept. of Cell, Molecular & Developmental Biology.
Advisor: Li Zeng.
Committee: Heber Nielsen, Gary Sahagian, and Linden Hu.
Keyword: Biology.read less - ID:
- bk128p13g
- Component ID:
- tufts:25415
- To Cite:
- DCA Citation Guide EndNote
