Effects of parathyroid hormone (PTH) and PTH-related peptide on expressions of matrix metalloproteinase-2, -3, and -9 in growth plate chondrocyte cultures

Endocrinology. 1998 Apr;139(4):2120-7. doi: 10.1210/endo.139.4.5941.


The roles of PTH and PTH-related peptide (PTH-rp) in the expression of matrix metalloproteinases (MMPs) during endochondral bone formation were investigated, using various cartilages obtained from young rabbits and rabbit chondrocyte cultures. Immunohistochemical, immunoblotting, zymographical, and/or Northern blot analyses showed that MMP-2 and -9 levels were much higher in the growth plate than in permanent cartilage in vivo. In growth plate chondrocyte cultures, PTH, PTH-rp, and (Bu)2cAMP increased the amount of MMP-2 present in the culture medium, as revealed by zymograms and immunoblots, whereas the other tested growth factors or cytokines, including bone morphogenetic protein-2 and interleukin-1, did not increase the MMP-2 level. PTH also increased the MMP-2 messenger RNA level within 24 h. In addition, PTH increased MMP-3 and -9 levels in the growth plate chondrocyte cultures. However, in articular chondrocyte cultures, PTH had little effect on the levels of MMP-2, -3, and -9. In contrast to PTH, interleukin-1 induced MMP-3 and -9, but not MMP-2, in growth plate and articular chondrocytes. These findings suggest that in ossifying cartilage, PTH/PTH-rp plays a pivotal role in the induction of various MMPs, including MMP-2 (which is considered to be a constitutive enzyme), and that PTH/PTH-rp is involved in the control of cartilage-matrix degradation during endochondral bone formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagenases / analysis
  • Collagenases / metabolism*
  • Gelatinases / analysis
  • Gelatinases / genetics
  • Gelatinases / metabolism*
  • Gene Expression / drug effects
  • Growth Plate / drug effects
  • Growth Plate / enzymology*
  • Humans
  • Interleukin-1 / pharmacology
  • Male
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 3 / metabolism*
  • Matrix Metalloproteinase 9
  • Metalloendopeptidases / analysis
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Parathyroid Hormone / pharmacology*
  • Parathyroid Hormone-Related Protein
  • Proteins / pharmacology*
  • RNA, Messenger / metabolism
  • Rabbits


  • Interleukin-1
  • PTHLH protein, human
  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Proteins
  • RNA, Messenger
  • Collagenases
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9