title: Association between the chondrocyte phenotype and the expression of adipokines and their receptors: evidence for a role of leptin but not adiponectin in the expression of cartilage-specific markers.
abstract: Although extensive evidence support the key role of adipokines in cartilage homeostasis, contradictory data have been found for their expression and their effects in chondrocytes. This study was then undertaken to determine whether a phenotypic modulation may affect the expression of adipokines and their receptors in human chondrocytes. The expression of leptin, adiponectin and their receptors, as well as cartilage-specific genes was examined in chondrocytes obtained from patients with osteoarthritis either directly after cells harvest or after culture in monolayer or in alginate beads. The results showed major changes in the gene expression pattern after culture in monolayer with a shift from the adipokines to their receptors. Interestingly, this downregulation of adipokines was associated with a loss of chondrocyte phenotype, and chondrocytes recovered a cartilage-like expression profile of leptin and adiponectin when cultured in a tridimensional chondrocyte phenotype-inducing system, but ceased expressing their receptors. Further experiments clearly showed that leptin but not adiponectin promoted the expression of cartilage-specific markers through mitogen-activated protein kinase, Janus kinase and phosphatidylinositol-3 kinase signaling pathways. In conclusion, our data indicate that any phenotypic modulation could affect chondrocyte responsiveness to leptin or adiponectin, and provide evidence for an important role for leptin in regulating the expression of cartilage-specific markers.
authors.affiliation: UMR CNRS-UHP 7561, Faculté de Médecine, Vandoeuvre-les-Nancy, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Francin
authors.forename: Cécile
authors.initials: C
authors.lastname: Guillaume
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Humbert
authors.forename: Pascale
authors.initials: P
authors.lastname: Pottie
authors.forename: Patrick
authors.initials: P
authors.lastname: Netter
authors.forename: Didier
authors.initials: D
authors.lastname: Mainard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Presle
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D054417:Receptors, Adipokine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D054392:Adipokines; D052242:Adiponectin; D015415:Biomarkers; D020738:Leptin; D054417:Receptors, Adipokine; D019869:Phosphatidylinositol 3-Kinases; D053612:Janus Kinases; D020928:Mitogen-Activated Protein Kinases