title: Differential effects of fibronectin fragment on proteoglycan metabolism by intervertebral disc cells: a comparison with articular chondrocytes.
abstract: METHODS
  This in vitro study used the alginate bead culture system to probe for differences in the effects of fibronectin fragment on cell proliferation and proteoglycan metabolism by different populations of intervertebral disc cells and articular chondrocytes.
  
  
  OBJECTIVE
  To compare the effects of fibronectin fragment on cell proliferation, and proteoglycan synthesis and degradation by cells from the nucleus pulposus, the anulus fibrosus, and articular cartilage.
  
  
  BACKGROUND
  In articular cartilage, the administration of fibronectin fragment stimulates cartilage degeneration. Fibronectin fragment levels were increased in human intervertebral discs with increased disc degeneration. Fibronectin fragment injected into the central region of the rabbit intervertebral disc induced a progressive degeneration of that disc.
  
  
  METHODS
  Bovine tails and metacarpophalangeal joints from 14- to 18-month-old animals were used. Alginate beads containing cells isolated from intervertebral discs and articular cartilage were cultured with (1-100 nmol/L) or without (control) fibronectin fragment in the presence of 10% fetal bovine serum. In these cultures, deoxyribonucleic acid and proteoglycan contents, as well as the rate of proteoglycan synthesis were determined. Proteoglycan degradation was measured in cultures with or without 10 nmol/L fibronectin fragment.
  
  
  RESULTS
  In articular chondrocytes, fibronectin fragment strongly suppressed proteoglycan synthesis and stimulated proteoglycan degradation; the total proteoglycan content was diminished in a dose-dependent manner. Compared to articular chondrocytes, nucleus pulposus cells responded to fibronectin fragments in a similar, although less pronounced manner. On the other hand, anulus fibrosus cells treated with fibronectin fragment did not show any significant effects on proteoglycan degradation. A slight but statistically significant up-regulation of proteoglycan synthesis was observed at 10 nmol/L fibronectin fragment in outer anulus fibrosus cells. However, total proteoglycan content was decreased significantly at high concentrations of fibronectin fragment.
  
  
  CONCLUSIONS
  Fibronectin fragment has different effects on cell proliferation, proteoglycan synthesis, degradation, and accumulation by articular chondrocytes and intervertebral disc cells. The different effects of fibronectin fragment in those different cell types suggest metabolic differences between these cells, and may further suggest differences in pathways of fibronectin fragment signaling as well as a differential need of these cells to be involved in tissue remodeling in which both anabolic and catabolic pathways might be altered.
authors.affiliation: Department of Orthopedic Surgery, Rush Medical College at Rush University Medical Center, Chicago, IL, USA.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Aota
authors.forename: Howard S
authors.initials: HS
authors.lastname: An
authors.forename: Gene
authors.initials: G
authors.lastname: Homandberg
authors.forename: Eugene J M-A
authors.initials: EJ
authors.lastname: Thonar
authors.forename: Gunnar B J
authors.initials: GB
authors.lastname: Andersson
authors.forename: Rajeswari
authors.initials: R
authors.lastname: Pichika
authors.forename: Koichi
authors.initials: K
authors.lastname: Masuda
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000008:administration & dosage / Q000494:pharmacology*; D007403:Intervertebral Disc / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008662:Metacarpophalangeal Joint; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013623:Tail; D015854:Up-Regulation
chemical_list: D005353:Fibronectins; D010446:Peptide Fragments; D011509:Proteoglycans