title: Expanding the adipokine network in cartilage: identification and regulation of novel factors in human and murine chondrocytes.
abstract: BACKGROUND
  Obesity is a major risk factor for a plethora of diseases including joint disorders associated with cartilage destruction. Recently, it has been demonstrated that adipose tissue might contribute to degenerative joint diseases via the secretion of potent bioactive molecules termed adipokines.
  
  
  OBJECTIVE
  To study expression of the novel adipokines chemerin, lipocalin 2 (LCN2) and serum amyloid A3 (SAA3) in murine and human chondrocytes, under basal conditions, in response to a range of biological and pharmacological treatments, and during chondrocyte differentiation.
  
  
  METHODS
  Chemerin, LCN2 and SAA3 mRNA and protein expression were evaluated by quantitative real-time reverse transcription PCR and western blot analysis, respectively, in the ATDC-5 murine chondrocyte cell line, a human immortalised chondrocyte cell line (T/C-28a2) and primary cultured human chondrocytes.
  
  
  RESULTS
  Human and murine chondrocytes expressed chemerin, LCN2 and SAA3 mRNA; interleukin (IL)-1β was a potent inducer of these novel adipokines. Moreover, dexamethasone, lipopolysaccharides (LPS) and other relevant adipokines such as leptin and adiponectin were able to modulate chemerin, LCN2 and SAA3 mRNA expression alone and when coadministered. Intracellular signal transducers involved in the IL-1β-mediated upregulation of LCN2 and SAA3 included Janus kinase (JAK) 2, phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein (MAP) kinases. Finally, expression of chemerin, LCN2 and SAA3 mRNA expression were modulated throughout chondrocyte differentiation.
  
  
  CONCLUSIONS
  Chemerin, LCN2 and SAA3 are implicated in chondrocyte pathophysiology, and regulated by other relevant factors that drive inflammatory process such as IL-1β, LPS and adipokines including leptin and adiponectin. It seems likely that JAK2, PI3K and MAP kinases are involved in mediating these responses.
authors.affiliation: Correspondence to Dr Oreste Gualillo, Santiago University Clinical Hospital, Research Laboratory 9 (NEIRID LAB, Laboratory of Neuro Endocrine Interactions in Rheumatology and Inflammatory Diseases). Building C, Level 2, Calle Choupana s/n, 15706, Santiago de Compostela, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Conde
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Gomez
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bianco
authors.forename: Morena
authors.initials: M
authors.lastname: Scotece
authors.forename: Pamela
authors.initials: P
authors.lastname: Lear
authors.forename: Carlos
authors.initials: C
authors.lastname: Dieguez
authors.forename: Juan
authors.initials: J
authors.lastname: Gomez-Reino
authors.forename: Francisca
authors.initials: F
authors.lastname: Lago
authors.forename: Oreste
authors.initials: O
authors.lastname: Gualillo
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics; D054392:Adipokines / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D053583:Interleukin-1beta / Q000494:pharmacology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000685:Serum Amyloid A Protein / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000209:Acute-Phase Proteins; D054392:Adipokines; D018925:Chemokines; D002630:Chemotactic Factors; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C478630:RARRES2 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; C489625:SAA3P protein, human; C076498:Saa3 protein, mouse; D000685:Serum Amyloid A Protein; C523686:chemerin protein, mouse; C071332:Lcn2 protein, mouse