Evidence of leptin involvement in OA

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Evidence of leptin involvement in OA

Sep 21, 2004 Veronique Duqueroy

Montreal, QC - Leptin, an adipocyte-derived hormone, may play an important

role in the pathophysiology of osteoarthritis (OA) and could be involved in

both cartilage destruction and repair processes, according 2 studies

presented yesterday at the 4th World Congress of the Global Arthritis

Research Network.

A link to obesity?

Dr Pascale Pottie (CNRS, , France) and colleagues reported a study

showing the contribution of leptin to cartilage changes associated with OA

[1]. The hormone, known to be a regulator of appetite and energy

expenditure, is secreted by the adipocytes and is suspected to be a

modulator of immune response and inflammatory processes.

Pottie et al found leptin in the synovial fluid of OA patients undergoing

joint replacement of the knee. " The concentrations of the hormone were well

correlated to the body mass index of these patients, " Pottie told the

meeting. Since obesity and being overweight constitute a risk factor for OA,

this suggests that leptin could be a metabolic factor implicated in OA, she

added.

The researchers also found that levels of leptin were also more elevated in

women than in men (12.95+8.92 µg/L vs 8.16+5.5 µg/L, respectively).

Leptin expression related to the grade of cartilage destruction

Cartilage biopsy from patients with OA revealed that leptin is overexpressed

in OA cartilage, " especially near the OA lesions, " Pottie continued. The

level of leptin expression was related to the grade of cartilage

destruction. " In cartilage with mild OA, 77% of the biopsy samples had low

leptin levels, whereas in cartilage with severe OA, 50% of the samples had

high leptin levels, " Pottie observed. " The more severe the OA lesion, the

more leptin is produced in cartilage, " she added.

The overexpression of leptin was noted in both fibrillated cartilage and

osteophytes of OA patients, while few chondrocytes produced leptin in normal

cartilage. When looking at the expression of growth factors such as IGF-1

and TGF-beta 1, " we had the same pattern of expression of leptin, " said

Pottie, which is increased levels.

The more severe the OA lesion, the more the leptin is produced in

cartilage.

Pottie et al also studied the effects of leptin on rat cartilage, after

administering intra-articular injections of various doses of the hormone

(10, 31, 100, and 300 µg) in the animal knee joints. At doses of 30 to 100

µg, there was a " stimulation of the proteoglycan anabolism, " while at the

100-µg dose, leptin significantly stimulated the growth-factor expressions

in cartilage, Pottie reported.

A modest increase of proinflammatory mediator production

A poster from Dr Crofford (University of Michigan, Ann Arbor) et al

presented at the same meeting brought deeper insight on the role of leptin

in arthritis [2]. The researchers tried to determine whether leptin alters

production of eicosanoid and proinflammatory cytokines. They used primary

human synovial cells of patients with RA or OA collected at the time of

surgery. The overnight treatment of the fibroblasts with 100 ng/mL of leptin

led to a modest increase of the production of IL-6 and IL-8. The

prostaglandin E2 levels were modestly increased only when compared with

IL-1beta as a positive control. The authors concluded, " Leptin affects the

production of proinflammatory mediators and enhances inflammation in

patients with arthritis. "

Agent of destruction or repair?

Leptin may have " an ambiguous behavior, such as IL-6, " Pottie commented to

rheumawire. It could be involved in the destruction of the cartilage, she

said, noting that leptin has a marked expression in lesion areas and also

enhances eicosanoid and proinflammatory cytokines, but at the same time, it

may also be involved in proliferation (increased leptin levels in

osteophytes) and reparation (stimulation of the proteoglycan metabolism).

" My personal feeling is that leptin attempts to repair the cartilage, "

Pottie told rheumawire. The next step for her team is to further investigate

the effect of leptin injections and to compare normal and OA chondrocytes in

vitro.

Sources

1. Pottie P, Presle N, Dumond H, et al. Is leptin the link between

obesity and osteoarthritis? Arthritis Res Ther 2004; 6(Suppl 3):8

Available at:

2. http://arthritis-research.com/content/6/S3/8 Crofford LJ, Mehta HH,

Roessler BJ, Mancuso P. Leptin induces production of eicosanoids and

proinflammatory cytokines in human synovial fibroblasts. Arthritis Res

Ther 2004; 6 ((Suppl 3)):64. Available at:

http://arthritis-research.com/content/6/S3/64