Type
Text
Type
Dissertation
Advisor
Rubin, Clinton T | Judex, Stefan | Chan, Mei Lin E | Hamrick, Mark.
Date
2016-12-01
Keywords
bone marrow, cell tracking, mesenchymal stem cells, satellite cells, skeletal muscle, vibration | Biomedical engineering -- Biomechanics
Department
Department of Biomedical Engineering
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/76965
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
In excess, adipogenesis and adiposity can compromise the quality of the musculoskeletal system, disrupt progenitor cell populations, and increase susceptibility to diabetes. The extent to which muscle and bone tissue are impaired by obesity-related pathologies is not clear. Additionally, while fat, bone, and muscle are distinct tissue systems, the degree to which bone marrow cells contribute to the fat/muscle phenotype in the pre-obese state is yet to be elucidated. To combat obesity, exercise is a common treatment modality that is anabolic to bone and muscle and catabolic to fat. However, compliance is low, obese patients may be unable to exercise due to physical limitations, and it can be unsafe for those at risk of fracture. As a surrogate for exercise, our lab has demonstrated the ability of mechanical stimulation in the form of low intensity vibration (LIV) to bias mesenchymal stem cell (MSC) differentiation away from the fat differentiation pathway. Influencing cell differentiation and/or migration patterns may aid in protecting musculoskeletal tissue systems disrupted by obesity-related complications. To establish a systemic fat insult, eight week C57Bl/6J male mice were subject to either OVX surgery (sham surgery controls) or a 45% high fat diet (regular diet controls) for 10wk. LIV treatment (0.25-3g, 90Hz, 15-30min/day, 5day/wk) was administered to OVX animals for 6wk, and high-fat diet or regular diet animals for 8wk. High-fat and regular animals were also subject to bone marrow transplantations for bone marrow cell tracking purposes. OVX increased adipogenic gene expression in the muscle while high-fat diet increased intermuscular lipid accumulation by 717%, quantified using oil red O staining. Other alterations in the muscular niche include the compromised satellite cell populations in OVX and increased expression of PKCθ in high-fat diet, which influences insulin signaling and demonstrates the negative consequences of an adipose burden on the muscle niche. Bone marrow-derived cells did not contribute to the intermuscular adiposity seen in high-fat diet animals. However, both bone marrow-derived cells and donor MSCs were accelerated to the visceral fat pads of animals on 10wk of high-fat diet, contributing to the expansion of the fat pad. These findings emphasize the notable changes in the musculature and bone marrow populations that precede changes in body habitus leading to obesity, and also the significance of the interactions of bone with muscle and fat tissues. Mechanical stimulation in the form of LIV was effective in mitigating muscular adiposity in both OVX and high-fat animal models and demonstrates the ability to be useful as a therapeutic intervention in preventing the onset of obesity or type II diabetes. | In excess, adipogenesis and adiposity can compromise the quality of the musculoskeletal system, disrupt progenitor cell populations, and increase susceptibility to diabetes. The extent to which muscle and bone tissue are impaired by obesity-related pathologies is not clear. Additionally, while fat, bone, and muscle are distinct tissue systems, the degree to which bone marrow cells contribute to the fat/muscle phenotype in the pre-obese state is yet to be elucidated. To combat obesity, exercise is a common treatment modality that is anabolic to bone and muscle and catabolic to fat. However, compliance is low, obese patients may be unable to exercise due to physical limitations, and it can be unsafe for those at risk of fracture. As a surrogate for exercise, our lab has demonstrated the ability of mechanical stimulation in the form of low intensity vibration (LIV) to bias mesenchymal stem cell (MSC) differentiation away from the fat differentiation pathway. Influencing cell differentiation and/or migration patterns may aid in protecting musculoskeletal tissue systems disrupted by obesity-related complications. To establish a systemic fat insult, eight week C57Bl/6J male mice were subject to either OVX surgery (sham surgery controls) or a 45% high fat diet (regular diet controls) for 10wk. LIV treatment (0.25-3g, 90Hz, 15-30min/day, 5day/wk) was administered to OVX animals for 6wk, and high-fat diet or regular diet animals for 8wk. High-fat and regular animals were also subject to bone marrow transplantations for bone marrow cell tracking purposes. OVX increased adipogenic gene expression in the muscle while high-fat diet increased intermuscular lipid accumulation by 717%, quantified using oil red O staining. Other alterations in the muscular niche include the compromised satellite cell populations in OVX and increased expression of PKCθ in high-fat diet, which influences insulin signaling and demonstrates the negative consequences of an adipose burden on the muscle niche. Bone marrow-derived cells did not contribute to the intermuscular adiposity seen in high-fat diet animals. However, both bone marrow-derived cells and donor MSCs were accelerated to the visceral fat pads of animals on 10wk of high-fat diet, contributing to the expansion of the fat pad. These findings emphasize the notable changes in the musculature and bone marrow populations that precede changes in body habitus leading to obesity, and also the significance of the interactions of bone with muscle and fat tissues. Mechanical stimulation in the form of LIV was effective in mitigating muscular adiposity in both OVX and high-fat animal models and demonstrates the ability to be useful as a therapeutic intervention in preventing the onset of obesity or type II diabetes. | 130 pages
Recommended Citation
Frechette, Danielle, "The contribution of bone marrow cells to the formation of bone, fat, and muscle, a commitment disrupted by systemic distress and normalized by mechanical stimulation" (2016). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2833.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2833