title: 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.
authors.affiliation: Department of Orthopaedics, 98 Hospital of PLA, Zhejiang, 313000, Huzhou, China. wangcy1228@163.com
authors.forename: Chao-Yang
authors.initials: CY
authors.lastname: Wang
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Yang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Tan
authors.forename: Shun-Min
authors.initials: SM
authors.lastname: Xing
authors.forename: De-Chun
authors.initials: DC
authors.lastname: Chen
authors.forename: Sheng-Ming
authors.initials: SM
authors.lastname: Xu
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
mesh_terms: D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D011485:Protein Binding; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C493716:Runx2 protein, mouse