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ACL Deficiency Modifies Topographical Degradation in Posttraumatic Osteoarthritis

Award Number: R01AR069047
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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¿ DESCRIPTION (provided by applicant): Trauma is one of the leading etiologic factors for knee osteoarthritis. In addition to blunt impact to articular cartilage, trauma often damages other tissues in the joint, such as meniscus, anterior cruciate ligament (ACL), and subchondral bone. Such damage can introduce a cascading series of adverse events that leads to the onset and progression of posttraumatic osteoarthritis (PTOA). A lack of quantitative imaging-based biomarkers is preventing an accurate assessment of early tissue degradation after traumatic injury. The long-term goal of our research is to apply the imaging-based biomarkers to detect the early degradation of cartilage and subchondral bone during the progression of osteoarthritis, so that clinical outcomes can be improved. The objective in this project is to apply several sophisticated and quantitative imaging parameters to determine the signature events at the molecular and morphological levels associated with PTOA, using a rabbit model. The central hypothesis is that a simultaneous presence of ACL-deficiency and trauma accelerates the adverse events in tissue degeneration when compared to impact alone or ACL-deficiency alone. Guided by strong preliminary data, the central hypothesis will be tested by pursuing two specific aims: (1) Map the topographical degradations of ultrastructure and molecular/imaging biomarkers in both femoral and tibial articular cartilage and subchondral bone after a single impact in rabbit knee, at three time delays after the impact; and (2) Determine the acceleration of the combined effect of single impact and ACL-deficiency on the topological degradations in articular cartilage and subchondral bone. Under the first aim, a cascade series of cellular, molecular, ultrastructural and morphological degradation in both articular cartilage and subchondral bone will be mapped out topographically over the joint surface, depth-dependently across different structural zones, and at high resolutions. Under the second aim, the acceleration of tissue degradation under the influence of the combined effect of both trauma and ACL-deficiency will be determined quantitatively. At the conclusion of this preclinical study, a se of multidisciplinary parameters that have the ability to predict and monitor PTOA progression will be identified and quantified at high resolution. This project is both significant and innovative, because it puts these advanced parameters to use, for the first time, to investigate the acceleration of PTOA progression under the influence of ACL damage. We will gain a solid foundation on the complex mechanism in PTOA. The proposed project is the critical step in a continuum of research that is expected to lead to the development of clinical and pharmacological strategies that will forestall the tissue degradation and allow differential treatments for simple damage vs. complex damages by trauma.


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	2022	OAKLAND UNIVERSITY	2200 N SQUIRREL RD	ROCHESTER	MI	48309	OAKLAND	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	4/17/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	OAKLAND UNIVERSITY	2200 N SQUIRREL RD	ROCHESTER	MI	48309	OAKLAND	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	2/13/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $394,772 )
2022	2022	OAKLAND UNIVERSITY	2200 N SQUIRREL RD	ROCHESTER	MI	48309	OAKLAND	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	5/3/2022	NON-COMPETING CONTINUATION	$35,891
2022	2022	OAKLAND UNIVERSITY	2200 N SQUIRREL RD	ROCHESTER	MI	48309	OAKLAND	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	3/24/2022	NON-COMPETING CONTINUATION	$358,881
														Subtotal = $394,772

Issue Date FY: 2021 ( Subtotal = $430,226 )
2021	2021	OAKLAND UNIVERSITY	2200 N SQUIRREL RD	ROCHESTER	MI	48309	OAKLAND	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	6/25/2021	NON-COMPETING CONTINUATION	$31,048
2021	2021	OAKLAND UNIVERSITY	2200 N SQUIRREL RD	ROCHESTER	MI	48309	OAKLAND	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	3/31/2021	NON-COMPETING CONTINUATION	$399,178
														Subtotal = $430,226

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	OAKLAND UNIVERSITY	2200 N SQUIRREL RD	ROCHESTER	MI	48309	OAKLAND	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	5/1/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $443,531 )
2019	2019	OAKLAND UNIVERSITY	2200 N SQUIRREL RD	ROCHESTER	MI	48309	OAKLAND	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	3/7/2019	NON-COMPETING CONTINUATION	$443,531
														Subtotal = $443,531

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2017	OAKLAND UNIVERSITY	2200 N SQUIRREL RD	ROCHESTER	MI	48309	OAKLAND	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	4/27/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $443,531 )
2017	2017	OAKLAND UNIVERSITY	2200 N SQUIRREL RD	ROCHESTER	MI	48309	OAKLAND	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	6/1/2017	NON-COMPETING CONTINUATION	$443,531
														Subtotal = $443,531

Issue Date FY: 2016 ( Subtotal = $500,170 )
2016	2016	OAKLAND UNIVERSITY	110 NORTH FOUNDATION HALL	ROCHESTER	MI	48063		USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	2/17/2016	NEW	$500,170
														Subtotal = $500,170

Grand Total All Awards = $2,212,230

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ACL Deficiency Modifies Topographical Degradation in Posttraumatic Osteoarthritis

Award Number: R01AR069047

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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