Leveraging New Approach Methodologies and Non-Animal Technologies to Accelerate Osteoarthritis Research

Post Date: August 29, 2025

Expiration Date: August 29, 2026

We invite research grant applications that utilize New Approach Methodologies (NAMs) and Non-Animal Technologies (NATs)—such as archived human joint tissues, organoids, tissue chips, advanced in vitro systems, computational and mathematical models, and non-invasive imaging techniques. When appropriately justified, applications may also incorporate combinations of these approaches with animal models, including genetically modified mouse models and underutilized large animal models, to investigate the biological mechanisms driving the initiation and progression of osteoarthritis (OA).

While aging and obesity are important risk factors for OA, research efforts in the past have focused primarily on the more advanced stages of OA. Relatively little is understood about the initial changes triggering disease etiology and early progression. While traditional animal models remain essential for scientific discovery, emerging technologies present unique advantages that—when applied effectively or in combination—can significantly broaden the research toolkit, enabling scientists to tackle biomedical questions that were previously impossible to address. The National Institutes of Health (NIH) is launching the NAM/NAT initiative to prioritize innovative, human-relevant science while promoting a reduction in animal use. This effort aligns with the U.S. Food and Drug Administration’s (FDA) recent commitment to minimizing reliance on animal testing for drug development.

Examples of possible topics include, but are not limited to:

• Molecular characterization of joint degeneration phenotypes.
• Age-related changes in chondrogenic stem cells and their role in OA onset.
• Age-related metabolic changes contributing to OA development.
• Influence of the aging immune system on OA initiation.
• Early alterations at the chondro-osseous junction.
• Interactions between inflammatory signals and joint, bone, and synovial responses.
• Role of pro-inflammatory molecules in cartilage degradation
• Signaling pathways mediating inflammation-driven joint degeneration.
• Mechanotransduction pathways linking physical loading to gene expression in joints.
• Contributions of non-cartilaginous joint tissues (nerves, synovium, muscle, fat, tendon) to OA pathology.
• Mapping genetic loci and downstream effectors involved in joint degeneration.
• Roles of cellular senescence and aging-associated epigenetic changes.
• Gene-gene and gene-environment interactions influencing OA susceptibility.
• Mechanisms by which physical activity may alleviate OA symptoms.
• Integration of regenerative medicine and rehabilitation strategies.
• Development of regenerative rehabilitation approaches to enhance tissue repair and functional recovery in patients with knee OA.