Differential protein and mRNA expression of CaMKs during osteoclastogenesis and its functional implications

Biochem Cell Biol. 2012 Aug;90(4):532-9. doi: 10.1139/o2012-002. Epub 2012 Mar 19.

Abstract

The calmodulin-dependent kinase (CaMK) family has been recently recognized to participate in the regulation of osteoclastogenesis. However, there are some controversial reports regarding the mRNA expression patterns of CaMKs during osteoclastogenesis, although the protein expression pattern of most CaMKs during osteoclastogenesis have not been studied. In the present study, we attempted to address this issue by using a mouse bone marrow monocyte model and parallel Western blotting and quantitative real-time PCR. Our results revealed some interesting expression patterns of CaMKs during the process. Among all CaMKs examined, only CaMKIIδ exhibited consistent expression patterns between its mRNA and protein with both rising remarkably during osteoclastogenesis. CaMKIV protein was not detectable during the first three days of cell culture, but it rose on Day 5. The CaMK inhibitor, KN93, subdued osteoclastogenesis during the first three days of cell culture, a time when CaMKIV was absent while other KN93-sensitive CaMKs presented. In addition, KN93 was found to inhibit the expression of some early receptor activator of NF-κB (RANK) signaling intermediates (extracellular signal-regulated kinase (ERK) and Akt) in the non-differentiated mouse bone marrow monocytes. Collectively, these data reveal differential expression patterns of KN93-sensitive CaMK proteins and their mRNAs during osteoclastogenesis, supporting a CaMKII-RANK signaling interaction in the regulation of early osteoclastogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzylamines / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / metabolism
  • Osteoclasts / cytology*
  • Osteoclasts / metabolism
  • RNA, Messenger / metabolism*
  • Receptor Activator of Nuclear Factor-kappa B / genetics
  • Receptor Activator of Nuclear Factor-kappa B / metabolism
  • Sulfonamides / pharmacology

Substances

  • Benzylamines
  • RNA, Messenger
  • Receptor Activator of Nuclear Factor-kappa B
  • Sulfonamides
  • Tnfrsf11a protein, mouse
  • KN 93
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Camk2d protein, mouse
  • Extracellular Signal-Regulated MAP Kinases