Expression and regulation of CCN genes in murine osteoblasts

Bone. 2006 May;38(5):671-7. doi: 10.1016/j.bone.2005.10.005. Epub 2005 Nov 28.


Members of the CCN family of genes include cysteine-rich 61 (CYR61), connective tissue growth factor (CTGF), nephroblastoma overexpressed (NOV), and Wnt-induced secreted proteins (WISP) 1, 2 and 3. CCN proteins play a role in cell differentiation and function, but their expression and function in skeletal tissue is partially understood. We examined the expression and regulation of CCN genes in primary cultures of murine osteoblasts treated with transforming growth factor beta (TGFbeta), bone morphogenetic protein (BMP)-2, or cortisol. Northern blot analysis revealed the presence of CYR61, CTGF, NOV, and WISP 1 and 2 transcripts in murine osteoblasts, but not WISP 3 transcripts. Northern and Western blot analyses revealed that TGF beta, BMP-2, and cortisol increased CYR61 and CTGF mRNA and protein levels. TGF beta decreased NOV and increased WISP 2 mRNA and protein levels, and TGF beta and BMP-2 increased, whereas cortisol decreased WISP 1 mRNA and protein levels. Nuclear run-on assays revealed that TGF beta, BMP-2 and cortisol enhanced CYR61 and CTGF transcription, TGF beta and BMP-2 induced and cortisol suppressed WISP 1, and TGF beta induced WISP 2 transcription. Suppression of NOV transcription could not be detected due to low control levels. In conclusion, five of the six known CCN genes are expressed by osteoblasts and their transcription is regulated by TGF beta, BMP-2 and cortisol.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / metabolism
  • Bone Morphogenetic Proteins / pharmacology
  • Cells, Cultured
  • Connective Tissue Growth Factor
  • Gene Expression Regulation*
  • Hydrocortisone / metabolism
  • Hydrocortisone / pharmacology
  • Immediate-Early Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Mice
  • Nephroblastoma Overexpressed Protein
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Transcription, Genetic / drug effects
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology


  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • CCN2 protein, mouse
  • Ccn3 protein, mouse
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Nephroblastoma Overexpressed Protein
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor
  • Hydrocortisone