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Role of Hormones on Bundle-Specific ACL Function in the Growing Knee Joint

Award Number: R01AR071985
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2018
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Role of Hormones on Bundle-Specific ACL Function in the Growing Knee Joint - PROJECT SUMMARY Anterior cruciate ligament (ACL) injuries impact more than 250,000 people in the U.S. annually. Sex is a major risk factor for ACL injury during adolescence, but not in childhood or adulthood. To explain the increased injury risk for females, several modifiable and non-modifiable risk factors have been explored. Very few of these studies examine the impact on the ACL tissue itself, which in turn, can impact injury risk or the need for patient-specific treatment. The long-term goal of our work is to explore mechanisms by which sex and skeletal growth impact ACL structure, function, injury risk, and treatment. Our prior work has established sex- and region-specific differences in function and cross-sectional area (CSA) within its anteromedial (AM) and posterolateral (PL) bundles. These differences appear around early adolescence and persist as adolescence progresses. Yet, the mechanism driving such sex-specific tissue adaptations is unclear. Earlier initiation of puberty has been associated with greater cumulative estrogen exposure, which may influence ACL bundle function. Additionally, ACL injury risk varies during the menstrual cycle in humans, but the presence of corresponding changes in ACL bundle size and function is unknown. Additionally, a direct relationship between temporal hormone levels and ACL size and function has not been established. Thus, the objective of this proposal is to determine how sex hormones impact ACL bundle size and function. To accomplish this objective, we will leverage our multi- disciplinary experience to accomplish the following aims. Aim 1 examines effect of puberty onset on long-term ACL bundle size and function. In Aim 1a, we will assess how timing of natural puberty onset influences long- term ACL bundle size and function throughout adolescence. In Aim 1b, we will assess whether early induction of puberty and rise in estrogen further alters ACL bundle size and function throughout adolescence. Aim 2 examines the effect of cyclic hormone levels on short-term ACL bundle size and function. In Aim 2a, we will assess how cyclic sex hormone levels influence ACL bundle size and function throughout the normal estrus cycle. In Aim 2b, we will assess whether stabilization of hormone levels reduces cyclic changes in ACL bundle size and function. If successful, this proposal will establish a clear and direct link between natural changes in sex hormones during adolescence and ACL size or function. Ultimately, the information gained can suggest promising human clinical trials of injury risk reduction and new potential treatment strategies.


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: 2025 ( Subtotal = $630,473 )
2025	2025	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27695	WAKE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	7	3/27/2025	NON-COMPETING CONTINUATION	$584,974
2025	2025	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27695	WAKE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	7	5/7/2025	NON-COMPETING CONTINUATION	$45,499
2025	2024	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27695	WAKE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	6	2/25/2025	COMPETING CONTINUATION	$1,219
2025	2022	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27695	WAKE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	2/25/2025	NON-COMPETING CONTINUATION	-$1,219
														Subtotal = $630,473

Issue Date FY: 2024 ( Subtotal = $654,883 )
2024	2024	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27695	WAKE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	5/8/2024	COMPETING CONTINUATION	$654,883
														Subtotal = $654,883

Issue Date FY: 2022 ( Subtotal = $321,137 )
2022	2022	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27607	WAKE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	5/26/2022	NON-COMPETING CONTINUATION	$29,195
2022	2022	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27607	WAKE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	3/25/2022	NON-COMPETING CONTINUATION	$291,942
														Subtotal = $321,137

Issue Date FY: 2021 ( Subtotal = $316,336 )
2021	2021	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27607	WAKE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	4/12/2021	NON-COMPETING CONTINUATION	$316,336
														Subtotal = $316,336

Issue Date FY: 2020 ( Subtotal = $351,131 )
2020	2020	NORTH CAROLINA STATE UNIVERSITY	2701 SULLIVAN DR STE 240	RALEIGH	NC	27695	WAKE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	3/13/2020	NON-COMPETING CONTINUATION	$351,131
														Subtotal = $351,131

Issue Date FY: 2019 ( Subtotal = $350,104 )
2019	2019	NORTH CAROLINA STATE UNIVERSITY	2701 SULLIVAN DR STE 240	RALEIGH	NC	27695	WAKE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	4/3/2019	NON-COMPETING CONTINUATION	$350,104
														Subtotal = $350,104

Issue Date FY: 2018 ( Subtotal = $337,663 )
2018	2018	NORTH CAROLINA STATE UNIVERSITY	2701 SULLIVAN DR STE 240	RALEIGH	NC	27695	WAKE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	9/19/2018	SUPPLEMENT FOR EXPANSION	$14,151
2018	2018	NORTH CAROLINA STATE UNIVERSITY	2701 SULLIVAN DR STE 240 CAMPUS BX 7514	RALEIGH	NC	27695	WAKE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/23/2018	NEW	$323,512
														Subtotal = $337,663

Grand Total All Awards = $2,961,727

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Role of Hormones on Bundle-Specific ACL Function in the Growing Knee Joint

Award Number: R01AR071985

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2018

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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