Monday, August 23, 2010


Subcellular relocation of histone deacetylase 4 regulates growth plate chondrocyte differentiation through Ca2+/calmodulin-dependent kinase IV.

"histone deacetylase 4 (HDAC4) is located in the nucleus of chondrocytes in the proliferation zone and relocates to the cytoplasm of chondrocytes in the prehypertrophic zone in vivo. The relocation of HDAC4 from the nucleus to the cytoplasm may play a role during chondrocyte differentiation. Expression of active CaMKIV in chondrocytes promotes HDAC4 relocation into cytoplasm in primary chondrocytes. Conversely, HDAC4 relocation is blocked by a Ca(2+)/calmodulin-dependent kinase IV (CaMKIV) inhibitor. This indicates that CaMKIV signaling plays an important role in regulating HDAC4 relocation. In addition, CaMKIV is required for HDAC4 phosphorylation, which is required for HDAC4 association with the cytoplasmic protein 14-3-3. Active CaMKIV also stimulates runt-related transcription factor-2 (RunX2) and type X collagen (Col X) promoter activities and overcomes repression of these promoter activities by HDAC4. Furthermore, CaMKIV increases gene expression of the chondrocyte differentiation markers Ihh and Col X. Our results demonstrate that CaMKIV induces chondrocyte differentiation through regulation of HDAC4 subcellular relocation, from the nucleus to the cytoplasm, which results in increased activity of RunX2 and transition of chondrocytes from the proliferative to the prehypertrophic stage."

Can CAMK4 be manipulated to increase height?

"HDAC4 null mice display premature ossification of developing bones due to ectopic and early onset chondrocyte hypertrophy.  This is associated with a loss of inhibition of the activity of runt-related transcription factor-2 (RunX2), a transcription factor necessary for chondrocyte hypertrophy during endochondral bone formation."

"activation of CaMKIV prevents nuclear entry of HDAC4 and enhances the binding of HDAC4 to the cytoplasmic binding protein 14-3-3 in a phosphorylation-dependent manner."

"CaMKIV is strongly expressed in prehypertrophic chondrocytes where HDAC4 is located to the cytoplasm. On the other hand, CaMKIV is weakly expressed in proliferating chondrocytes where HDAC4 is located in the nucleus. This indicates that CaMKIV may be involved in dynamic regulation of HDAC4 translocation between the cytoplasm and the nucleus in chondrocytes."

No comments:

Post a Comment