PCAF acetylates Runx2 and promotes osteoblast differentiation

Abstract

Osteoblasts play a crucial role in bone formation. However, the molecular mechanisms involved in osteoblast differentiation remain largely unclear. Runt-related gene 2 (Runx2) is a master transcriptional factor for osteoblast differentiation. Here we reported that p300/CBP-associated factor (PCAF) directly binds to Runx2 and acetylates Runx2, leading to an increase in its transcriptional activity. Upregulation of PCAF in MC3T3-E1 cells increases the expression of osteogenic marker genes including alkaline phosphatase (ALP), osteocalcin (Ocn), and Osteopontin (Opn), and ALP activity was stimulated as well. Consequently, the mineralization of MC3T3-E1 cells was remarkably improved by PCAF. In contrast, PCAF knockdown decreases the mRNA levels of ALP, Ocn, and Opn. ALP activity and the mineralized area were attenuated under PCAF knockdown conditions. These results indicate that PCAF is an important regulator for promoting osteoblast differentiation via acetylation modification of Runx2.

A Positive Role of MicroRNA‐15b on Regulation of Osteoblast Differentiation

“…2A). ALP and type 1 collagen are early osteoblast differentiation markers genes (Gutierrez et al, 2002; Jensen et al, 2009; Monroe et al, 2012; Wang et al, 2013). To further confirm these findings, C3H10T1/2 cells were transfected with negative control or miR-15b inhibitor in the presence of osteogenic medium.…”

“…Since expression of osteoblast differentiation marker genes and osteoblast mineralization were regulated by miR-15b (Fig. 2), and Runx2 activity can be altered by the post translational mechanisms such as acetylation, ubiquitination, phosphorylation, protein-protein interactions (Jeon et al, 2006; Wang et al, 2013; Boumah et al, 2009; McGee-Lawrence et al, 2013; Lengner et al, 2005), we determined Runx2 protein expression. Human MSCs were transiently transfected with either negative control or miR-15b inhibitor and were allowed to differentiate them.…”

Impact of electromagnetic fields on stem cells: common mechanisms at the crossroad between adult neurogenesis and osteogenesis

“…In particular, signaling molecules such as bone morphogenetic proteins (BMPs) and Wnt pathway favor osteoblastogenesis, while Notch1 and its downstream target Hes1 inhibit osteoblast differentiation. Recently, it has been shown that the transcriptional factor Runx2, a major target of BMP pathway, induces osteoblast differentiation by repressing Hes1 and by activating OC and other bone-related genes (Ann et al, 2011; Wang et al, 2013). …”

Chromatin modifiers and histone modifications in bone formation, regeneration, and therapeutic intervention for bone-related disease

“…Transgenic overexpression of Wdr5 using a 2.3-kb α (1)I-collagen promoter induced accelerated osteoblast and chondrocyte differentiation resulting in substantially increased endochondral bone growth suggesting [63]. Several other acetyltransferases have been implicated in epigenetic regulation of bone formation, osteoblast-related gene expression or deregulated in osteoarthritis including PCAF (KAT2B) [60, 64], MOZ/MORF (KAT6A/KAT6B) [65, 66], and the circadian-rhythm specific acetyltransferase: Clock (KAT13D) [67]. …”