Notice of Special Interest: Mechanisms of Osteoarthritis

Notice Number: NOT-AG-24-002

Deadline: This notice applies to due dates on or after June 5, 2024 and subsequent receipt dates through May 8, 2027


This Notice of Special Interest (NOSI) invites applications on research employing genetically defined and/or modified mouse models, other animal models such as dogs and monkeys, or archived human joint tissues to explore the biological mechanisms underlying the initiation and progression of osteoarthritis (OA). Osteoarthritis is a significant problem in the aging population and is a major contributor to mobility limitations endemic in this population and, therefore, is an important element in the research mission of NIA and NIAMS. Inflammatory processes are evident in aging and advanced stages of osteoarthritis and are likely to be major contributors to the chronic pain that is the most common symptom of the condition. The initiating factor(s) responsible for OA are controversial. For the purposes of this announcement, osteoarthritis is distinguished from other joint diseases, such as rheumatoid arthritis, in which inflammation arising from autoimmunity is the primary cause of tissue damage. The root causes of joint degeneration in osteoarthritis remain unclear, but there are three widely accepted routes: aging, traumatic injury, and obesity.

While aging is an important risk factor for osteoarthritis, research efforts in the past have focused primarily on the more advanced stages of osteoarthritis. Relatively little is understood about the initial changes triggering disease etiology and early progression. This NOSI is intended to encourage novel approaches to accelerate development and characterization of emerging or under-explored models as well as testing hypotheses that will lead to an improved understanding of the origins and mechanisms (both mechanical and molecular) mediating osteoarthritic progression or testing various therapeutic interventions for osteoarthritis.

Suggested research topics may include, but are not limited to:

  • Molecular characterization of disease pathology phenotypes in joint degeneration;
  • Understanding the age-related changes in chondrogenic stem cells and their potential influence on the etiology of osteoarthritis;
  • Characterization of changes at the chondro-osseous junction that precede or accompany degradation of the articular surface;
  • The role of the aging immune system in the initiation of OA;
  • Defining the relationship between inflammatory signals and biological responses in joints, subchondral bone, and synovial tissue;
  • Identifying signaling pathways triggered by joint inflammation and their roles in joint degeneration;
  • Understanding the age-related changes in metabolism that facilitate the initiation and/or progression of OA;
  • Understanding the role of pro-inflammatory molecules associated with joint degradation and/or progression of OA;
  • Investigating molecular signals that link mechanical loading with gene expression and the effects of that signaling on joint health;
  • Understanding the role of joint non-articular cartilage tissues (nerves, synovium, muscle, fat, tendon etc.) to OA disease initiation and progression;
  • Mapping of genetic loci linked to joint degeneration;
  • Identification of downstream effectors in pathways mediating effects of gene inactivation or transgene expression in joint degeneration;
  • Defining the role of cellular senescence and aging-associated epigenetic changes on OA onset and progression;
  • Determining contributions of gene-gene and gene-environment interactions to overall genetic influence on OA susceptibility;
  • Using genetically modified animals and genomic analysis tools to understand the genetic components (including noncoding variants) involved in joint degeneration and to develop approaches for treating and preventing disease;
  • Identification of molecular mechanisms by which physical activity may ameliorate OA symptoms;
  • Studying the relationship between regenerative medicine and rehabilitation; and
  • Developing regenerative rehabilitation approaches to optimize self-healing and functional tissue recovery when combined with regenerative protocols for patients with knee osteoarthritis.

For more information, please see the opportunity webpage.