Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases

Wang, Hui; Litherland, Gary J.; Elias, Martina S.; Kitson, Gareth I; Cawston, Tim E.; Rowan, Andrew D.; Young, David A.

doi:10.1136/annrheumdis-2011-200372

Cited by 191 publications

(180 citation statements)

References 52 publications

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“…Interestingly, leptin secretion was 40 % lower and adiponectin was increased by 70 % in IPFP cells compared with the subcutaneous adipose tissue [73]. Moreover, it was demonstrated that the culture media from OA patients' IPFP adipocytes induced MMP13 and MMP1 expression in articular chondrocytes and that the leptin level positively correlated with the expression of both MMPs and cartilage collagen destruction [20]. The end-stage OA patients' fat pad cells also showed an increased expression of inflammatory cytokines and down-regulation of anabolic peptides, such as VCAM1 (vascular cell adhesion molecule-1), CTGF (connective tissue growth factor) and CD44 (cluster of differentiation) [74].…”

Section: Adipocytokines Secretion By Infrapatellar Fat Padmentioning

confidence: 84%

“…These proteins have been detected in synovial fluid (SF) and the plasma of patients with OA [16][17][18]. A putative source of adipocytokine secretion in the region of the knee joint is the infrapatellar fat pad (IPFP) [19,20]. In addition, recent findings indicate that deteriorated articular cartilage is another source of adipocytokines within the joint [21].…”

Section: Introductionmentioning

confidence: 99%

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The role of adipocytokines in the pathogenesis of knee joint osteoarthritis

Richter

Trzeciak

Owecki

et al. 2015

International Orthopaedics (SICOT)

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Osteoarthritis (OA) is one of the most common causes of musculoskeletal disability in the world. Traditionally, it has been thought that obesity contributes to the development and progression of OA by increased mechanical load of the joint structures. Nevertheless, studies have shown that adipose tissue-derived cytokines (adipocytokines) are a possible link between obesity and OA. Furthermore, according to recent findings, not only articular cartilage may be the main target of these cytokines but also the synovial membrane, subchondral bone and infrapatellar fat pad may be encompassed in the process of degradation. This review presents the most recent reports on the contribution of adipocytokines to the knee joint cartilage degradation, osteophyte formation, infrapatellar fat pad alterations and synovitis.

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Section: Adipocytokines Secretion By Infrapatellar Fat Padmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

The role of adipocytokines in the pathogenesis of knee joint osteoarthritis

Richter

Trzeciak

Owecki

et al. 2015

International Orthopaedics (SICOT)

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“…24 25 In a recent in vitro study, leptin, either alone or in synergy with interleukin 1, significantly induced collagen release from cartilage by upregulating collagenolytic and gelatinolytic activity. 26 Some preliminary epidemiological studies have suggested a potential role of circulating leptin in OA. While Iwamoto reported that serum leptin concentration might be related to increases in body weight and total fat mass in postmenopausal women with knee OA, 27 Miller reported that decreases in serum leptin could explain why weight loss improved physical function and symptoms in patients with knee OA.…”

Section: Discussionmentioning

confidence: 99%

Cross-sectional and longitudinal associations between circulating leptin and knee cartilage thickness in older adults

et al. 2013

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Objective To investigate cross-sectional and longitudinal associations between serum leptin levels and knee cartilage thickness in older adults. Methods A prospective cohort of 163 randomly selected subjects (mean 63 years, range 52-78, 46% women) was studied. Knee cartilage thickness at medial tibial, lateral tibial, femoral and patellar sites was determined using T1-weighted fat-suppressed MRI. Serum leptin levels were measured by radioimmunoassay. Radiographic osteoarthritis, body fat (%), trunk fat (%), weight and height were measured, and body mass index (BMI) was calculated. Results Cross-sectionally, serum levels of leptin were negatively associated with femoral (β: −0.013, 95% CI −0.022 to −0.003), medial tibial (β: −0.009, 95% CI −0.018 to −0.001), lateral tibial (β: −0.012, 95% CI −0.021 to −0.003) and patellar (β: −0.014, 95% CI −0.026 to −0.002) cartilage thickness after adjustment for covariates. Moreover, BMI, trunk fat and total body fat were negatively associated with cartilage thickness, and the significant associations disappeared after further adjustment for leptin. Longitudinally, both baseline leptin and change in leptin were associated with greater changes in medial tibial cartilage thickness (β: −0.004, 95% CI −0.007 to −0.001 and β: −0.009, 95% CI −0.018 to −0.001, respectively) in multivariable analyses. Conclusions Serum levels of leptin are independently and consistently associated with reduced cartilage thickness cross-sectionally and longitudinally. In addition, the associations between adiposity measures and cartilage thickness are mediated by leptin, suggesting leptin may play a key role in cartilage thinning.

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“…These findings showed that leptin might play a positively protective role against the destructive course of arthritis. However, Hui et al [110] found that leptin coming from joint white adipose tissue could trigger cartilage degradation by promoting and activating the matrix metalloproteinases. Leptin served as a proinflammatory adipokine with a catabolic role on cartilage metabolism by raising proteolytic enzymes and working synergistically with other proinflammatory stimuli.…”

Section: Cellular Studies Concerning the Effect Of Leptin On Cartilagementioning

confidence: 99%

Emerging role of leptin in rheumatoid arthritis

Tian

Liang

Wang

et al. 2014

Clinical and Experimental Immunology

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SummaryNumerous studies have suggested the importance of leptin against autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) and psoriasis. To summarize our current understanding of the role of leptin in inflammatory responses and rheumatoid arthritis (RA), a systematic review was conducted to assess the discrepancy of leptin in RA and its effect on immunity according to different studies. Recently, emerging data have indicated that leptin is involved in the pathological function of RA, which is common in autoimmune disorders. This review discusses the possible consequences of leptin levels in RA. Blocking the key signal pathways of leptin and inhibiting the leptin activity-like leptin antagonist may be a promising way for potential therapeutic treatment of RA at risk of detrimental effects. However, leptin was increased in patients with RA and may also regulate joint damage. Thus, more understanding of the mechanism of leptin in RA would be advantageous in the future.

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Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases

Cited by 191 publications

References 52 publications

The role of adipocytokines in the pathogenesis of knee joint osteoarthritis

The role of adipocytokines in the pathogenesis of knee joint osteoarthritis

Cross-sectional and longitudinal associations between circulating leptin and knee cartilage thickness in older adults

Emerging role of leptin in rheumatoid arthritis

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