Cytokines From Adipose Tissue: New OA Drug Targets

Oct 14, 2013

ACR2013: Research continues to implicate the obesity-associated molecule leptin as a factor in osteoarthritis, independent of the mechanical effects of body weight. Factors that control leptin show promise as future treatments.

The evidence ever more strongly implicates the cytokines produced by adipose tissue, rather than simply the added load that obesity imposes on joints, in the damage of osteoarthritis (OA). Research to be presented at the American College of Rheumatology meeting later this month describes factors that regulate the obesity-associated molecule leptin as important to the severity of OA, and point towards new drug targets.

The link to leptin is not new; previous studies have shown the molecule to be a proinflammatory factor in synovial tissue. What's new are insights into the controls behind leptin. A team at the University of Turku in Finland will report that many physiological factors (BMI, age, sex, diabetic status, and radiographic indicators of OA) are unrelated to the proinflammatory effects of leptin. But the action of one specific regulatory molecule called SOSC-3 (suppressor of cytokine signaling 3) specifically dampened these leptin effects in in vitro studies on cartilage samples from patients scheduled for knee replacement. (Abstract 44: Suppressor Of Cytokine Signaling 3 Negatively Modulates Leptin-Mediated Catabolic and Proinflammatory Effects In Cartilage)

More evidence that leptin's effects are independent of obesity comes from a study of 275 patients undergoing total knee or hip arthroplasty at Geneva University Hospital in Switzerland. Those who reported continuing neuropathic pain two years after surgery (and half were likely to say that they wouldn't undergo the procedure again) had shown significantly higher preoperative blood levels of leptin, whether or not they were obese. (Abstract 2133: Neuropathic Pain After Primary Total Hip and Knee Arthroplasty)

Levels of all four adipokines (adiponectin, adipsin, leptin, and resistin) appear to vary by gender, and may hold clues to subtypes of osteoarthritis, according to a 78-patient study from the Arthritis Program at Toronto Western Hospital. After adjustment for age, BMI, and nature of joint involvement, higher levels of leptin and adiponectin, and lower levels of adipsin were significantly associated with a greater regional joint count among women with osteoarthritis. Among men, only resistin levels differed significantly in association with joint pain. The associations appeared to be a dose-response relationship, the researchers say, and the results suggest an impact on comorbidities. (Abstract 244: Association Between Serum Adipokine Levels and Extent Of Symptomatic Joint Involvement In Hip and Knee Osteoarthritis) .