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Regulation of Axin2-expressing cells in the adult tendon

Award Number: R01AR079495
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: 06/15/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Regulation of Axin2-expressing cells in the adult tendon - A significant portion of the population is affected by tendon injuries. Due to limited regenerative potential, these injuries are complicated by slow and imperfect healing. In order to develop therapies to improve healing outcomes, it is important to understand the mechanisms regulating adult tendon cells during homeostasis and healing. Tendon-derived stem/progenitor cells have been identified in vitro and display stem/progenitor characteristics, including clonogenicity, multilineage differentiation potential, and self-renewal. However, the identity and activity of resident progenitor populations in the adult tendon are not well understood. We have identified an adult tendon cell marked by Axin2-CreERt2 that displays progenitor-like activities in vitro and in vivo. After tendon injury, Axin2+ cells proliferate, infiltrate the injury site, and express Scx-GFP. In addition, we find their injury response is dependent upon the Wnt pathway. We propose to use lineage tracing, genetic loss of function, and next generation sequencing techniques to gain a mechanistic understanding of Axin2+ cells in the adult tendon during homeostasis and healing. We will test the hypothesis that Axin2+ cells are a unique tendon cell population that, through Wnt secretion and response, are key orchestrators of tendon healing. First, we will test the function of Wnt signaling in maintaining Axin2+ progenitor cell identity during homeostasis. Next, we will define the function of Wnt secretion and canonical Wnt signaling in regulating Axin2 cell injury response at early and later stages of tendon healing. We will also test if activation of canonical Wnt signaling promotes Axin2+ cell identities and injury response, leading to improved healing outcomes. A mechanistic understanding of Axin2+ cell function is an integral step towards expanding our fundamental understanding of adult tendon biology. This knowledge could impact the design of new therapies to improve tendon healing in patients.


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 = $437,131 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	5/7/2025	NON-COMPETING CONTINUATION	$31,545
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	4/23/2025	NON-COMPETING CONTINUATION	$405,586
														Subtotal = $437,131

Issue Date FY: 2024 ( Subtotal = $462,245 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	5/20/2024	NON-COMPETING CONTINUATION	$462,245
														Subtotal = $462,245

Issue Date FY: 2023 ( Subtotal = $476,542 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	5/17/2023	NON-COMPETING CONTINUATION	$476,542
														Subtotal = $476,542

Issue Date FY: 2022 ( Subtotal = $493,542 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	6/10/2022	NEW	$493,542
														Subtotal = $493,542

Grand Total All Awards = $1,869,460

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Regulation of Axin2-expressing cells in the adult tendon

Award Number: R01AR079495

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: 06/15/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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