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Obesity, cartilage mechanics, and joint health

Award Number: R01AR088065
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: 08/20/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Obesity, cartilage mechanics, and joint health - Abstract Osteoarthritis (OA) is a debilitating disease that affects 27 million adults in the U.S. A critical risk factor for OA is obesity, which increases the likelihood of developing OA 10-fold. Our prior work demonstrates that individuals with obesity exhibit changes in articular cartilage structure, composition, and function, consistent with early OA. Specifically, in response to a cartilage stress test, we found significantly greater cartilage strains following walking in individuals with obesity compared to normal weight participants in both the tibiofemoral and patellofemoral joints. Similarly, elevated T1rho relaxation times were found in both joints, indicative of a decrease in proteoglycan content and potentially impaired capacity to withstand loading. While it is well established that both weight loss and exercise improve OA symptoms, the mechanisms for these improvements remain unclear. Specifically, it is unknown whether these interventions can reverse the degenerative cartilage changes associated with obesity. Our preliminary data in individuals with obesity suggests that weight loss may improve cartilage composition (assessed via T1rho relaxation times) and improve serum biomarkers of cartilage health. Additionally, our preliminary data demonstrates the feasibility of decreasing compressive cartilage strain with an exercise intervention in those with rheumatoid arthritis. Thus, the proposed research seeks to address the central hypothesis that weight loss and exercise can each reverse obesity associated cartilage degeneration. We will first evaluate the effects of activity on cartilage degeneration cross sectionally in individuals with obesity (Aim 1) and then evaluate longitudinally the influence of weight loss or exercise in insufficiently active individuals with obesity (Aim 2). For participants in both Aims, we will quantify in vivo cartilage strain distributions in response to a treadmill stress test. Additionally, we will assess cartilage resilience, a novel biomarker with strong predictive ability for identifying OA, by probing the time required for cartilage to recover from loading. Noninvasive biomarkers of cartilage matrix integrity will also be measured using MRI (T1rho and T2 relaxation times). Finally, we will relate these changes in cartilage mechanics and composition to systemic biomarkers (serum/urine) of cartilage metabolism and inflammation. While both exercise and weight loss are established means to improve OA symptoms in individuals with obesity, the mechanisms for these improvements remain unknown. The proposed research will address a critical gap in knowledge by determining whether obesity-related degenerative changes in cartilage (reflective of early OA) can be reversed through weight loss or exercise. Since OA is traditionally thought of as irreversible, identifying interventions that reverse cartilage degeneration would represent a significant breakthrough for the millions suffering from this devastating disease.


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 = $675,318 )
2026	2026	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/19/2026	NEW	$675,318
														Subtotal = $675,318

Grand Total All Awards = $675,318

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Obesity, cartilage mechanics, and joint health

Award Number: R01AR088065

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: 08/20/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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