Anabolic Effects of Peniel 2000, a Peptide That Regulates Tgf-β1 Signaling on Intervertebral Disc Degeneration
2013
Study Design. An in vitro study with bovine intervertebral
disc(IVD) cells and an in vivo study with a rabbit
discdegeneration model on the
extracellular matrixmetabolism by a
biglycan-derived peptide (Peniel 2000; P2K). Objective. To investigate the mechanism for P2K-induced increases in
extracellular matrixand in vitro and in vivo effects of the peptide on IVD. Summary of Background
Data.
Transforminggrowth factor-β (TGF-β) has a functional versatility on the metabolism of IVD cells, suggesting that the regulation of TGF-β signaling is important in IVD degeneration. P2K was explored by an in silico drug discovery strategy to regulate TGF-β signaling. Methods. The putative target of P2K was verified by Biacore 3000 analysis and affinity purification using biotin-P2K. A monolayer culture system of bovine IVD cells was used to demonstrate the mechanism underlying the
anaboliceffects of P2K.
Smadsignaling and
extracellular matrixmetabolism of the IVD cells were investigated by Western blot and reverse transcription-polymerase chain reaction, respectively. The in vivo effect of P2K on degenerated
discwas investigated using a rabbit model of
discdegeneration. In 14 New Zealand white rabbits,
discdegeneration was induced by percutaneous annular punctures. After 4 weeks, 3 consecutive
discsin the same animal were treated with 5% lactose or P2K per
disc. Twelve weeks after the treatment, the regenerative activity in the
discwas examined by radiography, magnetic resonance imaging, and biochemical and histological analyses. Results. Direct binding of P2K to an active form of TGF-β1 was shown.
Type II collagenand
aggrecanwere increased in TGF-β1/P2K–treated bovine IVD cells, compared with nontreated and TGF-β1–treated cells. Results. In in vivo analysis, a single injection of P2K increased the
discheight (P Conclusion. A novel peptide, P2K, regulating TGF-β1 signaling had an
anaboliceffect on bovine IVD cells and rabbit degenerated
discs. The results suggest that P2K has considerable potential as a treatment of
degenerative disc disease.
Keywords:
-
Correction
-
Source
-
Cite
-
Save
30
References
21
Citations
NaN
KQI