Effects of PTHrP on expression of MMP9 and MMP13 in sika deer antler chondrocytes

Cell Biol Int. 2013 Dec;37(12):1300-7. doi: 10.1002/cbin.10168. Epub 2013 Sep 12.

Abstract

Deer antlers are the only mammalian appendages to display an annual cycle of full regeneration. However, little is known about the molecular mechanisms of antler regeneration. Our previous study has demonstrated that parathyroid hormone-related peptide (PTHrP) can promote proliferation of antler chondrocytes and inhibit its differentiation, but the mechanism underlying such regulation is not fully understood. We have determined the role of PTHrP on the mRNA expression of matrix metalloproteinase-9 (MMP9) and MMP13 in the antler chondrocytes. The possible pathways that transduce PTHrP effects were examined. In situ hybridization showed that MMP9 and MMP13 were mainly localized in the dermal fibroblasts, perichondrium, and cartilage in the sika deer antler, of which MMP9 and MMP13 were highly expressed in the chondrocytes. Exogenous PTHrP could inhibit the expression of MMP9 and MMP13 in the antler chondrocytes. The inhibitory effect of PTHrP on MMP9 was abolished by JNK inhibitor, SP600125, while P38MAPK inhibitor SB203850 and PKC inhibitor GF109203X could rescue the inhibitory effect of PTHrP on MMP13. The results suggest that PTHrP can inhibit MMP9 expression by JNK signaling pathway and MMP13 expression by p38MAPK and PKC signaling pathways in the antler chondrocytes. Thus PTHrP is involved in the control of antler chondrocytes maturation and cartilage matrix degradation.

Keywords: MMP; PTHrP; chondrocyte; sika deer antler.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthracenes / pharmacology
  • Chondrocytes / cytology
  • Chondrocytes / drug effects*
  • Chondrocytes / enzymology
  • Deer / genetics*
  • Deer / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic / drug effects*
  • In Situ Hybridization, Fluorescence
  • Indoles / pharmacology
  • Male
  • Maleimides / pharmacology
  • Matrix Metalloproteinase 13 / genetics*
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism
  • Parathyroid Hormone-Related Protein / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Anthracenes
  • Enzyme Inhibitors
  • Indoles
  • Maleimides
  • Parathyroid Hormone-Related Protein
  • pyrazolanthrone
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 9
  • bisindolylmaleimide I