Kelsey H. Collins Wins NEXT Award for Research on Fat-Osteoarthritis Relationship

The 2026 New Emerging eXperts in Translational Science (NEXT) Award has been granted to Kelsey H. Collins, Ph.D., for her research on the way fat tissue can contribute to osteoarthritis (OA). While OA has been categorized as a “wear and tear” condition associated with aging, Dr. Collins’ translational studies demonstrate that OA may be a systemic condition influenced by metabolic and immune factors, with fat being a key contributor to OA development and pain.

The most common type of arthritis, OA occurs when cartilage surrounding the ends of bone gradually wears away, resulting in joint pain and stiffness. OA affects more than 32.5 million Americans, typically impacting people older than 50 and those who have had a prior joint injury.ⁱ There is no cure for OA, but there are many successful treatment options. The estimated economic burden of OA has doubled in the last decade, reaching more than $136 billion annually.ⁱⁱ

“From a very young age, my mother struggled with an aggressive form of arthritis. At one point, she was told that she’d be wheelchair-bound, but biologic drugs changed her life,” Dr. Collins said. “I saw how the functional limitation and pain are what really matter to patients, and pain is something they must live and navigate with until they get a total joint replacement, or new solutions are created. As someone who struggled with knee injuries themselves, I wondered why there were no biologics or other therapies for OA. This gap in understanding, and the opportunity to think about biologic development for OA, was a space that I was very interested in when I started my career in research.”

Tracing How OA Develops

Since beginning her Ph.D. studies at the University of Calgary, Canada, under Walter Herzog, Ph.D., and continuing her postdoctoral work with Farshid Guilak, Ph.D., Dr. Collins focused her research on the ways adipose tissue (body fat) drives OA and pain. Her work has uncovered novel insights into the role of fat-derived factors involved in OA development and their interactions with fat-secreted factors and the immune system. However, she began this path through her work in human movement biomechanics research.

Dr. Collins’ interest in how obesity drives OA stems from her formative experiences as a trainee on the Alberta Innovates Health Solutions OA Team, where Dr. Herzog and other key opinion leaders in the field— including committee member Cyril Frank, M.D.—led an interdisciplinary initiative to develop new OA solutions. In one of these team meetings, Gillian Hawker, M.D., determined that a key target population was missing—the role of obesity and multi-morbidity—on OA pathogenesis. Concurrently, Dr. Guilak, who eventually became Dr. Collins’ postdoc mentor, and Tim Griffin, Ph.D., a postdoc at the time, had recently published cutting-edge work showing that obese mice that lacked certain signals like leptin were protected from OA.ⁱⁱⁱ Leptin is a hormone secreted by fat that is responsible for satiety (the feeling of being full after eating), but scientists now understand its pro-inflammatory actions in OA. Collectively, these events inspired Dr. Collins to further investigate this relationship.

To understand the mechanistic influence of systemic adipose (fat outside the joint) on the joint and how to identify communication mediators between fat and joints, Dr. Collins and her team designed and adapted obesity models and tools to report changes in serum (a fluid in blood plasma) and synovial fluid (a fluid that lubricates articular cartilage) with obesity and injury.

Dr. Collins and other researchers hypothesized that OA is actually a whole-body disease of pain and loss of physical function resulting from fat outside the joints. This focus creates a new research area to define adipose-derived factors that drive OA and pain, and potentially to identify new drivers, therapeutic candidates, and treatment strategies.

As excess fat tissue has been associated with OA development, Dr. Collins wanted to determine whether body fat rather than body mass drives OA development. Her approach was a rat model of diet-induced obesity, utilizing a high-fat/high sucrose “Western-type” obesity-inducing diet, which is similar to a Western-type diet.^iv,v In a validation study, obese rats that underwent anterior cruciate ligament transection, sham, or no surgery all had knee joint damage, demonstrating that diet alone could drive OA in this model.

As in humans, rats in the high-fat diet “Western-type” rat model exhibited variable, random responses to weight gain, yet still gained fat, resulting in some rats gaining fat without increasing body weight. These obesity-resistant rats were compared to rats that responded to diet by gaining both mass and body fat.^vi This rat model was used to understand how body fat and body mass are related to OA disease without an injury at 12 and 28 weeks. It was shown that western-type diet can drive damage. The researchers observed significant correlations between body fat percentage and the Modified Mankin Score—the odds of achieving a top score for OA damage—indicating a strong association between body fat and knee joint damage in diet-induced obesity. These findings further suggest the relationship between obesity and OA is not simply a problem of mechanical overloading. These studies also corroborated a role for leptin.

“In medicine, practitioners manage diseases with the best solution available at the time,” Dr. Collins stated. “When people have knee pain, the assumption is that it is driven by something isolated to the knee, and it is intuitive in most practices to think about the patient’s age. However, when we and others started asking questions about whether sex differences, obesity status, and aging can drive differential trajectories or phenotypes of disease, we saw patterns suggesting that perhaps OA is not an endpoint of all these things that are systemic and instead, maybe it can drive these multi-morbidities and even drive aging. With these data, our hope is that people will start to think a bit bigger about the importance of managing OA as a central node of whole patient health.”

Fat Tissue and Fat-Derived Factors as OA Drivers

Dr. Collins’ research then sought to determine how fat influences other tissues, such as the knee joint, to drive OA development. The research team developed a fat-free mouse model of lipodystrophy (LD)—a condition where there is complete or partial loss of fat tissue. To test the relationship between adipose tissue and its secretory factors on cartilage pathology, they superimposed an injury, mimicking OA, by destabilizing the medial meniscus. While LD mice exhibit many clinical signs of OA as observed in obesity—including inflammation and muscle weakness—these mice are protected from cartilage damage and pain when challenged with DMM. This allowed Dr. Collins and her team to begin determining how adipose tissue affects the joint. The protection was seen in male and female mice, even when challenged with DMM and a high-fat diet, showing this protection from a lack of fat tissue cannot be overridden by diet or sex.

In further research, Dr. Collins’ team found that susceptibility to cartilage damage and pain with DMM can be reintroduced in LD mice through a small fat graft, demonstrating adipose tissue and its associated paracrine signaling (a process where cells secrete signaling molecules into the surrounding environment to influence nearby target cells) are mediators of joint degeneration. These findings identify some new candidate therapeutic factors, and further corroborate existing factors, like leptin. Importantly, they are among the first to demonstrate the role of adipose tissue in OA and the development of musculoskeletal pain, supporting the hypothesis that OA may have systemic origins that indeed involve adipose tissue outside the joint.^vii

“Dr. Guilak taught me that the best way to prove yourself right is to try to prove yourself wrong,” Dr. Collins said. “We have all these technologies now that enable unbiased discovery, allowing us to step back and determine if the patterns we find support our findings on their own. My mentors have not been afraid of new tricks, and I’ve been trained in environments where people aren’t threatened by a new and better understanding of how OA develops.”

For future work, Dr. Collins plans to break down the interface between fat signaling, obesity, and aging to find more novel molecular drivers of pain and validate those identified in her mouse studies. Once the molecular, cellular, or nervous system factors responsible for the joint crosstalk driving OA have been determined, cell-based regenerative medicine approaches and new biologic drugs can be developed.

Funding for the NEXT Award is provided by the American Academy of Orthopaedic Surgeons and the Orthopaedic Research Society (ORS).

An independent 501(c)3 nonprofit, the Orthopaedic Research and Education Foundation strives to improve clinical care and patient outcomes by advancing research, developing new investigators, and uniting the orthopedic community in promoting musculoskeletal health. The Foundation raises funds to support research on diseases and injuries of bones, nerves, muscles, and tendons, and to enhance clinical care leading to improved health, increased activity, and a better quality of life for patients.

With more than 39,000 members, AAOS is the world’s largest medical association of musculoskeletal specialists. The organization advances musculoskeletal health by providing comprehensive education to help orthopedic surgeons and allied health professionals best treat patients in their daily practices. AAOS is the source for information on bone and joint conditions, treatments, and related musculoskeletal healthcare issues; and it leads the healthcare discussion on advancing quality.

References
ⁱ Arthritis Foundation. Osteoarthritis. https://www.arthritis.org/diseases/osteoarthritis. Accessed Jan. 12, 2026.
ⁱⁱ Hawker GA. 2019. Osteoarthritis is a serious disease. Clin Exp Rheumatol 37 Suppl 120:3-6.
ⁱⁱⁱ Griffin TM, Huebner JL, Kraus VB, Guilak F. Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis. Arthritis Rheum. 2009 Oct;60(10):2935-44. doi: 10.1002/art.24854. PMID: 19790050; PMCID: PMC2829313.
^iv Berenbaum F, Wallace IJ, Lieberman DE, et al. 2018. Modern-day environmental factors in the pathogenesis of osteoarthritis. Nat Rev Rheumatol 14:674-681.
^v Berenbaum F, Griffin TM, Liu-Bryan R. 2017. Review: Metabolic Regulation of Inflammation in Osteoarthritis. Arthritis Rheumatol 69:9-21.
^vi Collins KH, Hart DA, Reimer RA, et al. 2016. Response to diet-induced obesity produces time-dependent induction and progression of metabolic osteoarthritis in rat knees. J Orthop Res 34:1010-1018.
^vii Collins KH, Haugen IK, Neogi T, Guilak F. Osteoarthritis as a systemic disease. Nat Rev Rheumatol. 2026 Feb;22(2):105-117. doi: 10.1038/s41584-025-01332-8. Epub 2025 Dec 3. PMID: 41339496.