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Are we approaching a holistic view of leptin's role in arthritis?

  • O. Gualillo
    Affiliations
    SERGAS (Servizo Galego de Saude), IDIS-Santiago de Compostela (Health Research Institute of Santiago de Compostela), and the NEIRID (NeuroEndocrine Interactions in Rheumatic and Inflammatory Diseases) Group, Área Sanitaria de Santiago de Compostela e Barbanza, 15706, Santiago de Compostela, Spain
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Published:October 12, 2022DOI:https://doi.org/10.1016/j.joca.2022.10.005
      Adipokines—in particular, leptin, the forerunner of this superfamily—are receiving increasing attention for their role in exerting both beneficial and harmful actions in musculoskeletal inflammatory diseases. Leptin has been extensively associated with cartilage metabolism and OA. OA human chondrocytes have been shown to produce higher levels of leptin than normal cartilage
      • Dumond H.
      • Presle N.
      • Terlain B.
      • Mainard D.
      • Loeuille D.
      • Netter P.
      • et al.
      Evidence for a key role of leptin in osteoarthritis.
      , with the pattern of leptin expression related to the level of cartilage destruction
      • Ku J.H.
      • Lee C.K.
      • Joo B.S.
      • An B.M.
      • Choi S.H.
      • Wang T.H.
      • et al.
      Correlation of synovial fluid leptin concentrations with the severity of osteoarthritis.
      ,
      • Simopoulou T.
      • Malizos K.N.
      • Iliopoulos D.
      • Stefanou N.
      • Papatheodorou L.
      • Ioannou M.
      • et al.
      Differential expression of leptin and leptin’s receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism.
      . Moreover, elevated leptin levels have been found in serum, IPFP, synovial tissues, and cartilage of OA patients compared with healthy controls
      • Conde J.
      • Scotece M.
      • López V.
      • Abella V.
      • Hermida M.
      • Pino J.
      • et al.
      Differential expression of adipokines in infrapatellar fat pad (IPFP) and synovium of osteoarthritis patients and healthy individuals.
      ,
      • Scotece M.
      • Conde J.
      • Vuolteenaho K.
      • Koskinen A.
      • López V.
      • Gómez-Reino J.
      • et al.
      Adipokines as drug targets in joint and bone disease.
      . Accordingly, it has been demonstrated that leptin, in synergy with IL-1β, induces the expression of proinflammatory factors, such as IL-6, IL-8, NO, NOS2, PGE2, and COX2, in chondrocytes
      • Gomez R.
      • Scotece M.
      • Conde J.
      • Gomez-Reino J.J.
      • Lago F.
      • Gualillo O.
      Adiponectin and leptin increase IL-8 production in human chondrocytes.
      . It was recently demonstrated that leptin also regulates the production of IL-6, IL-8, and CCL3 by CD4+ T cells in OA patients, but not in healthy individuals
      • Scotece M.
      • Pérez T.
      • Conde J.
      • Abella V.
      • López V.
      • Pino J.
      • et al.
      Adipokines induce pro-inflammatory factors in activated Cd4+ T cells from osteoarthritis patient.
      , revealing new action mechanisms of leptin in the immune system and OA pathophysiology.
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