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Small molecule stimulation of lubricin for treatment of post-traumatic osteoarthritis

Award Number: R21AR082984
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: 08/15/2024
PERIOD OF PERFORMANCE END DATE: 08/14/2026

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Small molecule stimulation of lubricin for treatment of post-traumatic osteoarthritis - Project Summary/Abstract The prevalence and cost of osteoarthritis is astounding, with total osteoarthritis-attributable medical expenditures and lost earnings surpassing $300 billion in 2013, accounting for more than 10% of healthcare costs. The lack of disease modifying drugs for osteoarthritis is a significant challenge as they could be particularly beneficial in post-traumatic osteoarthritis (PTOA). This project aims to address this challenge using a novel phenotypic reporter-based system to identify FDA approved drugs that stimulate lubricin production by human chondrocytes. This novel drug target, lubricin, has proved effective in viral delivery to the mouse joint, preventing osteoarthritis. The ability to increase lubricin expression pharmacologically would be of significant value. Primary human articular chondrocytes were genetically engineered into lubricin reporter cells using a lentiviral vector. We have confirmed chondrogenic activity and correlation of lubricin expression with Gaussia luciferase expression. These cells will be used to screen FDA approved drugs for anabolic effects promoting lubricin expression in a physiologically inspired 3D cartilage model after simulated injury. Hit compounds will be those that significantly increase expression. We will then further investigate lubricin stimulation with hit compounds both in vitro and in vivo. A non-invasive knee injury model will be used to create an anterior cruciate ligament tear. This tear is a common sports injury which, even with repair, results in osteoarthritis in ~50% of cases. Our studies will treat the mice with intra-articular injections to establish lubricin stimulation as a potential disease modifying approach. The expected outcome of this research is to establish anabolic therapies promoting lubricin expression as a cure/preventative treatment for post-traumatic osteoarthritis. Mechanistic studies, confirming or identifying novel targets of FDA approved drugs in stimulation of lubricin will be performed. Ultimately, lubricin stimulation through a pharmacological approach, will be shown to be an effective method to prevent post-traumatic osteoarthritis in both a human in vitro model and an in vivo mouse model.


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 = $151,615 )
2025	2025	THE UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	8/29/2025	NON-COMPETING CONTINUATION	$151,615
2025	2024	THE UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	4/29/2025	NEW	$0
														Subtotal = $151,615

Issue Date FY: 2024 ( Subtotal = $206,844 )
2024	2024	THE UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/15/2024	NEW	$206,844
														Subtotal = $206,844

Grand Total All Awards = $358,459

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Small molecule stimulation of lubricin for treatment of post-traumatic osteoarthritis

Award Number: R21AR082984

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: 08/15/2024

PERIOD OF PERFORMANCE END DATE: 08/14/2026

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