Sunday, December 7, 2025 12/7/2025

Extracellular integration of a cohesive myotendinous junction

Award Number: R01AR081090
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: 01/16/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

Group Awards By:

View Award Description

Extracellular integration of a cohesive myotendinous junction - Force is transmitted from muscle to tendon across a specialized interface called the myotendinous junction (MTJ). The MTJ consists of transmembrane, intercellular and extracellular proteins that connect muscle to the cells and extracellular matrix (ECM) of tendon. The ECM is a 3D network of macromolecules that forms a continuum integrating muscle and tendon, facilitating the seamless transmission of force. The interdigitating interface of the MTJ is critical in force transmission from muscle to tendon and is hypothesized to reduce stress; nevertheless, MTJ injuries can arise from diverse events, including physical work, sports and trauma, which typically occur due to excessive eccentric force. Challenges in the clinical translation of engineering technologies targeted toward the muscle-tendon interface arise from the difficulty in integrating two disparate tissues to form a seamless MTJ. The objective of this proposal is to identify the role of the ECM and mechanical loading in establishing and maintaining the strong linkage between muscle and tendon. This knowledge will be essential for developing therapies to restore functionality to damaged MTJs. The proposed studies will test the hypothesis that the formation of a mechanically robust MTJ is dependent on the integration of ECM secreted by both muscle and connective tissue cells at the interface and is maintained by cyclic loading. We will test our hypothesis in two separate aims. In Aim 1, we will identify the cells and reciprocal interactions that establish an MTJ-specific ECM. We will use cell-specific metabolic labeling and proteomics to identify the components that muscle and connective tissue cells independently contribute to the MTJ (Aim 1a). Since it is currently technically infeasible to target the expression of MTJ-specific proteins only at the muscle-tendon interface in vivo, we will use in vitro co-cultures to investigate and perturb the reciprocal signaling between myogenic and connective tissue cells (Aim 1b). In Aim 2, we will determine role of mechanical forces in creating and maintaining a functional MTJ. First, we will directly investigate how embryonic motility affects development by using the muscular dysgenesis mouse model in which muscle contraction is abrogated (Aim 2a). Then we will directly compare how unloading (hindlimb suspension) and increased loading (treadmill training) affect the remodeling of ECM at the interface using metabolic labeling and proteomics. Next, we will generate 3D muscle-tendon constructs based on fibrin gels and cell-generated ECM (Aim 2b), since is not feasible to completely remove all mechanical forces in vivo. The constructs will enable us to test the effect of unloading, and static and cyclic loading on MTJ formation. Successful completion of the proposed studies will identify the extracellular parameters that establish and maintain the interface between muscle and tendon, which is essential for developing therapies to restore functionality to damaged MTJs.


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: 2026 ( Subtotal = $432,324 )
2026	2026	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	12/3/2025	NON-COMPETING CONTINUATION	$432,324
														Subtotal = $432,324

Issue Date FY: 2025 ( Subtotal = $435,527 )
2025	2025	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	12/20/2024	NON-COMPETING CONTINUATION	$435,527
														Subtotal = $435,527

Issue Date FY: 2024 ( Subtotal = $438,871 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	5/20/2024	SUPPLEMENT FOR EXPANSION	$118,380
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	1/22/2024	NON-COMPETING CONTINUATION	$297,363
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	2	5/29/2024	NON-COMPETING CONTINUATION	$23,128
														Subtotal = $438,871

Issue Date FY: 2023 ( Subtotal = $331,695 )
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	1/12/2023	NEW	$331,695
														Subtotal = $331,695

Grand Total All Awards = $1,638,417

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Extracellular integration of a cohesive myotendinous junction

Award Number: R01AR081090

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: 01/16/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer