High concentrations of fibronectin fragments cause short-term catabolic effects in cartilage tissue while lower concentrations cause continuous anabolic effects

Arch Biochem Biophys. 1994 Jun;311(2):213-8. doi: 10.1006/abbi.1994.1229.

Abstract

We reported earlier that Fn fragments (Fn-f) added to bovine articular cartilage cultured in serum-free DMEM cause marked elevated release of protease activity within a few days. This results in greatly elevated rates of release of proteoglycan (PG). We have now extended our studies to 4-week cultures of cartilage in the presence of 10% serum. We report here that cartilage cultured with 0.01, 0.1, and 1 microM of an amino terminal 29-kDa Fn-f in 10% serum accelerated the loss of PG from the tissue during the first few days in a concentration-dependent manner. However, beyond this period PG content decreased much more slowly. During this early period, the 29-kDa Fn-f decreased rates of protein and PG synthesis up to 50% in a concentration-dependent fashion. Beyond this period, the synthesis rates began to increase in a mode inversely related to 29-kDa Fn-f concentration, up to 135% of Fn-f free control values. However, during the entire culture period, cartilage cultured with 1 nM 29-kDa Fn-f had higher PG contents and had enhanced rates of protein and PG synthesis. Since 1 nM 29-kDa Fn-f stabilized cartilage against decreases in PG content, we tested its ability to block the activity of higher 29-kDa Fn-f concentrations. Cartilage was preincubated for 7 days with 1 nM 29-kDa Fn-f, and then the culture adjusted to 100 nM 29-kDa Fn-f to cause PG depletion. The preincubated cartilage showed markedly enhanced resistance to PG depletion. Since the protective effect was similar to known properties of IGF-1, the ability of 20 ng/ml IGF-1 to block against the effects of 100 nM Fn-f was tested and shown to be similar in magnitude to that of 1 nM 29-kDa Fn-f. We propose that the initial catabolic effects of higher concentrations of Fn-f, followed by the later anabolic effects, may aid in tissue repair. Also, the continuous anabolic effects of lower concentrations may be involved in tissue homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism*
  • Cattle
  • Cysteine / metabolism
  • DNA / metabolism
  • Endopeptidases / isolation & purification
  • Endopeptidases / metabolism*
  • Fibronectins / pharmacology*
  • Insulin-Like Growth Factor I / pharmacology
  • Kinetics
  • Methionine / metabolism
  • Molecular Sequence Data
  • Molecular Weight
  • Organ Culture Techniques
  • Peptide Fragments / pharmacology*
  • Proteoglycans / biosynthesis*
  • Recombinant Proteins / pharmacology
  • Sulfates / metabolism
  • Sulfur Radioisotopes
  • Time Factors

Substances

  • Fibronectins
  • Peptide Fragments
  • Proteoglycans
  • Recombinant Proteins
  • Sulfates
  • Sulfur Radioisotopes
  • Insulin-Like Growth Factor I
  • DNA
  • Methionine
  • Endopeptidases
  • Cysteine