title: Age-independent effects of hyaluronan amide derivative and growth hormone on human osteoarthritic chondrocytes.
abstract: OBJECTIVE
  Increased age is the most prominent risk factor for the initiation and progression of osteoarthritis (OA). The effects of human growth hormone (hGH) combined or not with hyaluronan amide derivative (HAD) were evaluated on human OA chondrocytes, to define their biological action and potentiality in OA treatment.
  
  
  METHODS
  Cell viability, metabolic activity, gene expression and factors released were tested at different time points on chondrocytes treated with different concentrations of hGH (0.01-10 μg/ml) alone or in combination with HAD (1 mg/ml).
  
  
  RESULTS
  We found that OA chondrocytes express GH receptor and that the different doses of hGH tested did not affect cell viability, metabolic activity or the expression of collagen type 2, 1, or 10 nor did it induce the release of IGF-1 or FGF-2. Conversely, hGH treatment increased the expression of hyaluronan receptor CD44. HAD combined with hGH reduced metabolic activity, IL6 release and gene expression, but not the suppressor of cytokine signaling 2 (SOCS2), which was significantly induced and translocated into the nucleus. The parameters analyzed, independently of the treatments used proportionally decreased with increasing age of the patients.
  
  
  CONCLUSIONS
  hGH only induced CD44 receptor on OA chondrocytes but did not affect other parameters, such as chondrocytic gene markers or IGF-1 or FGF-2 release. HAD reduced all the effects induced by hGH partially through a significant induction of SOCS2. These data show that GH or HAD treatment does not influence the response of the OA chondrocytes, thus the modulation of cellular response is age-independent.
authors.affiliation: a Laboratorio RAMSES , Istituto Ortopedico Rizzoli , Bologna , Italy .
authors.forename: Elena
authors.initials: E
authors.lastname: Gabusi
authors.affiliation: a Laboratorio RAMSES , Istituto Ortopedico Rizzoli , Bologna , Italy .
authors.forename: Francesca
authors.initials: F
authors.lastname: Paolella
authors.affiliation: a Laboratorio RAMSES , Istituto Ortopedico Rizzoli , Bologna , Italy .|b SC Laboratorio di Immunoreumatologia e Rigenerazione Tissutale , Istituto Ortopedico Rizzoli , Bologna , Italy , and.
authors.forename: Cristina
authors.initials: C
authors.lastname: Manferdini
authors.affiliation: b SC Laboratorio di Immunoreumatologia e Rigenerazione Tissutale , Istituto Ortopedico Rizzoli , Bologna , Italy , and.
authors.forename: Laura
authors.initials: L
authors.lastname: Gambari
authors.affiliation: c Fidia Farmaceutici S.p.A., Abano Terme , Padova , Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Schiavinato
authors.affiliation: a Laboratorio RAMSES , Istituto Ortopedico Rizzoli , Bologna , Italy .|b SC Laboratorio di Immunoreumatologia e Rigenerazione Tissutale , Istituto Ortopedico Rizzoli , Bologna , Italy , and.
authors.forename: Gina
authors.initials: G
authors.lastname: Lisignoli
mesh_terms: D000368:Aged; D000375:Aging; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000378:metabolism* / Q000473:pathology
chemical_list: D019382:Human Growth Hormone; D006820:Hyaluronic Acid
keywords: Age; chondrocytes; growth hormone; hyaluronan; osteoarthritis