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Spatial correlation of osteocyte gene response to local mechanical strain in bone tissue

Award Number: R21AR075937
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary There were more than 2 million osteoporotic fractures in the U.S. in 2005, which exceeded the incidence of heart attack, stroke, and breast cancer combined. Osteoporotic fractures are associated with a high level of mortality and morbidity; more than one in five patients who suffer a hip fracture will die within one year due to causes related to their injury. The annual medical costs exceeded $17 billion in 2005 and are expected to increase to $25 billion by 2025. Bone physiology and adaptation are regulated by mechanical loading, which alters gene and protein expression in bone cells. Mechanical loads on bone are sensed by osteocytes embedded in the bone that signal to progenitor cells on the bone surface and in the marrow. Experiments have identified threshold levels of bone strain and cell shear stress that trigger osteocyte signaling, but are generally aggregated over many cells or larger regions of bone. These measures provide limited information about the stochastic or variable nature of cell responses to load. In the near future, computational power will allow models of bone adaptation incorporating response to individual cell signaling molecules to be employed to explore bone physiology and predict the response of bone to new treatments. Such models will provide better insight into experimental and clinical data related to bone diseases. In anticipation of these models, the goal of this project is to measure the probability of expression of key signaling genes in osteocytes based on the local mechanical environment. The aims are to measure gene expression in bone subsequent to controlled loading in a bioreactor system, calculate the stress field using high-fidelity computational models, and perform spatial correlations to determine the likelihood of altered gene expression for a given mechanical environment.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	UNIVERSITY OF NOTRE DAME DU LAC	836 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	12/19/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $164,851 )
2021	2021	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	6/9/2021	NON-COMPETING CONTINUATION	$11,896
2021	2021	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	3/29/2021	NON-COMPETING CONTINUATION	$152,955
														Subtotal = $164,851

Issue Date FY: 2020 ( Subtotal = $185,715 )
2020	2020	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/18/2020	NEW	$185,715
														Subtotal = $185,715

Grand Total All Awards = $350,566

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Spatial correlation of osteocyte gene response to local mechanical strain in bone tissue

Award Number: R21AR075937

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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