Dr. Loeser’s team seeks to define the role of the gut microbiome in the pathogenesis of osteoarthritis (OA). OA is the most common form of arthritis, affecting over 27 million Americans, and is the #1 cause of chronic disability in adults. Management of OA is limited by the lack of interventions that slow disease progression. A better mechanistic understanding of OA is needed to develop new interventions that target mechanisms driving the disease process. Mounting evidence suggests that metabolic alterations, a systemic low grade pro-inflammatory state, and activation of the innate immune system play key roles in OA. These same factors have also been associated with altered composition of the gut microbiota (dysbiosis), which in turn is influenced by diet, in particular a high fat diet that contributes to obesity. We propose that dysbiosis of the gut microbiota, by promoting a chronic systemic pro-inflammatory state, can accelerate or worsen the development of OA when other risk factors, such as obesity or joint injury, are also present.
The unique multidisciplinary team of outstanding investigators will test the hypothesis that components of the gut microbiome contribute to the development of OA through activating innate immunity and promoting an inflammatory state. The success of these novel studies will have major public health implications. Defining a contribution of the gut microbiome to OA would indicate the use of microbiota profiling as a novel approach to identify individuals at risk of progressive OA and aid in the design of novel dietary, antibiotic, probiotic or prebiotic interventions to alter the specific components of the microbiome that contribute to OA progression.
In submitting publications, presentations and grant applications using data from your Phase I award, please remember to acknowledge the SOM Office of Research and TraCS Translational Team Science Award.
Collins Mbonu and Shahmeer Lateef join UNC TARC under the guidance of Dr. Leigh Callahan and Dr. Amanda Nelson, respectively. The purpose of the preceptorship program is to introduce medical and graduate students to rheumatology-related health care by supporting a full-time clinical or research experience in the broad area of rheumatic disease.
Jeffrey Brow and Nicolas Ashur are both MSTAR students who will work with Dr. Jordan this summer on a projects related to arthritis.
Jeffrey will work on a project looking at the role of obesity, diabetes mellitus, and cardiovascular disease as modulators of pain threshold in patients with symptomatic knee and hip osteoarthritis and Nicolas's project will explore the effect modification of co-morbidities on physical function in osteoarthritis.
Richard Loeser receives the OARSI Basic Science Research Award for "Aging and Osteoarthritis: What’s the Link?”
DELETION OF MACROPHAGE MIGRATION INHIBITORY FACTOR REDUCES SEVERITY OF OSTEOARTHRITIS IN MICE
Amanda Nelson and Yvonne Golightly:
VARIATIONS IN HIP SHAPE ARE ASSOCIATED WITH PREVALENT RADIOGRAPHIC KNEE OA: THE JOHNSTON COUNTY OSTEOARTHRITIS PROJECT
Antoine Baldassari and Leigh Callahan:
ASSOCIATIONS BETWEEN SOCIOECONOMIC STATUS AND RADIOGRAPHIC AND SYMPTOMATIC KNEE OSTEOARTHRITIS: DATA FROM THE OSTEOARTHRITIS INITIATIVE
Becki Cleveland and Leigh Callahan:
ASSOCIATION OF LARGE JOINT OSTEOARTHRITIS WITH ALL-CAUSE DEATH: THE JOHNSTON COUNTY OSTEOARTHRITIS PROJECT
PROGRESSION OF DISABILITY IS ASSOCIATED WITH SOCIOECONOMIC MEASURES IN THE JOHNSTON COUNTY OSTEOARTHRITIS PROJECT
Joanne M. Jordan:
A GENOME WIDE ASSOCIATION STUDY OF PRESSURE PAIN THRESHOLD IN THE JOHNSTON COUNTY OSTEOARTHRITIS PROJECT
Dr. Allen's abstract;
Knee osteoarthritis (OA) is a leading cause of pain and disability among veterans, and Department of Veterans Affairs health care users are the most severely affected. There is ample evidence that exercise improves pain, function, and other outcomes among patients with knee OA. However, the vast majority of individuals with knee OA are physically inactive. There is clearly a need to develop and implement programs that efficiently and effectively foster regular physical activity and improve key patient-centered outcomes among veterans with knee OA. This objective of this study is to evaluate the effectiveness a novel STepped Exercise Program for Knee OsteoArthritis (STEP-KOA).
This will be a randomized controlled trial of n=345 veterans with symptomatic knee OA in two VISN 6 sites, with participants assigned to two study arms: STEP-KOA and Arthritis Education Control (AE). STEP-KOA will begin with three months of access to a low-resource internet-based exercise training program that uses patient-specific information to determine and deliver an appropriate personalized exercise plan (Step 1). Participants who do not meet response criteria for clinically meaningful improvement in pain and function after three months of Step 1 will additionally receive telephone calls from an exercise counselor for three months, to facilitate adherence and address barriers to physical activity (Step 2). Participants who still fail to meet response criteria after Step 2 will receive in-person physical therapy visits, which address specific functional impairments and further tailor exercise recommendations (Step 3). Outcomes will be assessed at baseline, 3-months, 6-months, and 9 months (primary outcome time point). Veterans in the AE group will be offered participation in STEP-KOA after completing study assessments. The primary outcome will be the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), a measure of lower extremity pain, stiffness and function. The secondary outcomes will be objective measures of physical function. The main study analyses will compare the STEP-KOA intervention to the AE control condition at follow-up time points. We will also evaluate patient characteristics associated with the need for progression to each Step and will conduct a cost-effectiveness analysis of STEP-KOA. This stepped exercise intervention is matched with patient needs, and it also provides the VA with a potential approach for focusing limited physical therapy resources toward patients who do not respond adequately to initial, less resource intensive and costly strategies to improve physical activity and related outcomes.
Dr. Jordan will retain her current appointments as Joseph P. Archie, Jr. Eminent Professor of Medicine, Chief, Division of Rheumatology, Allergy and Immunology, and Director, Thurston Arthritis Research Center.
In her new role, Jordan will be charged with:
- Supervision of 5-year reviews of tenured faculty, department chairs and center directors
- Oversight of Appointment, Promotion and Tenure committees
- Faculty Pipeline Programs, the Simmons Scholar Program and the Scientific Integrity Office
- Coordination of searches for chairs and center directors
- Oversight of faculty leadership development activities in the School of Medicine
In her role as Executive Associate Dean, Jordan will report to Wesley Burks, MD, Executive Dean of the School of Medicine.
Jordan has served on the faculty of the UNC School of Medicine since 1987. The outstanding communications skills and leadership abilities she has displayed in her 27 years at UNC make her well suited for success in her new, expanded role. Jordan replaces Paul Godley, MD, PhD, who was recently appointed as the School’s Vice Dean for Finance and Administration.
All of us at UNC TARC and UNC RAI are so proud of Dr. Jordan!
Two of our very own clinical faculty, Dr. Maya Jerath and Dr. Bill Yount are two of only 22 doctors who are being awarded the 2015 UNC Health Care and Faculty Physicians Award for Carolina Care Excellence. Dr. Jerath and Dr. Yount are outstanding physicians who each achieved 100% satisfaction with their patients!
For those of us who know and love them, this comes as no surprise, but it is lovely that their excellent care is appreciated and recognized!
An R01 is a grant awarded by the NIH to support a large research project and they are hard to get. Dr. Golightly's RO1 is a four-year grant titled “The Role of Joint Hypermobility in Lower Body Osteoarthritis”, and her UNC TARC team includes Drs. Jordan, Nelson, Cleveland, Schwartz, and Renner; as well as Patrick Gale and Betsy Hackney. The project also has four researchers from other institutions; Duke, Harvard, and Hospital for Special Surgery.
Joint hypermobility is a condition in which range of motion at the joints is greater than normal and is commonly referred to as being “double-jointed.” Joint hypermobility is a lifelong condition that is common in youth and declines with age (joints tend to stiffen with age). As many as 25% of adults may have joint hypermobility, it is more common in women than men and may increase the risk for osteoarthritis (OA).
In the United States, the number of people diagnosed with OA is rapidly increasing each year, resulting in rising health care costs and more people experiencing disability.
We will be conducting the largest study to date of over 7,000 people from three large studies of participants with and without OA: the Johnston County Osteoarthritis Project, Genetics of Generalized Osteoarthritis study, and Genetics of Osteoarthritis study. This study will help us understand the role of joint hypermobility in lower body OA. Results of this study will lead to interventions, like shoes, bracing, or specialized exercises, that may promote good joint function to help prevent or treat OA.
“It is uncommon to get the award on the first try, and I feel very fortunate.”
UNC was well-represented at the North Carolina Rheumatology Association (NCRA) meeting March 21-22. Dr. Slavin did a fantastic case presentation sparking much discussion (photo). Dr. Jimmy Ford from pulmonary gave an excellent talk on pulmonary hypertension. Also in attendance were our fellows Drs. Adhikari and Ritt and Dr. Nelson who serves as the academic representative to the NCRA board.
Dr. Richard Loeser in the Division of Rheumatology, Allergy and Immunology and the UNC Thurston Arthritis Research Center has received a National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) research grant called a BIRT award for “Building Interdisciplinary Research Teams”. The purpose of this competitively reviewed award is for investigators holding a current NIAMS RO1 research project grant to form a new interdisciplinary team that will add a novel and innovative approach to the ongoing project. The new team members are Dr. Keith Burridge in the Department of Cell Biology and Physiology and Dr. Elizabeth Loboa in the Department of Biomedical Engineering. The team will study how cell receptors called integrins transmit signals that control the response of cartilage cells to mechanical forces. Cartilage is the tissue that coats the ends of bones providing a smooth and slippery surface that allows for normal joint motion. Maintenance of healthy cartilage is supported by a certain level of mechanical stimulation that occurs during normal joint use. However, abnormal and excessive forces on the cartilage, for example after a joint injury or in obese individuals, stimulate the cartilage cells to breakdown the cartilage, resulting in development of osteoarthritis, the most common form of arthritis and the number one cause of pain and disability in older adults. By better understanding the signals produced in response to various levels of force placed on cartilage cells, new therapies can be designed which would block the response seen with abnormal joint loading and promote the healthy responses needed for maintenance and repair.