Histone H3K9 Acetyltransferase PCAF Is Essential for Osteogenic Differentiation Through Bone Morphogenetic Protein Signaling and May Be Involved in Osteoporosis.
Human mesenchymal stem cells (MSCs) are multipotent progenitor cells that can differentiate into osteoblasts, chondrocytes, and adipocytes. The importance of epigenetic regulation for osteogenic differentiation of MSCs is widely accepted. However, the molecular mechanisms are poorly understood. Here, we show that histone H3K9 acetyltransferase PCAF plays a critical role in osteogenic differentiation of MSCs. Knockdown of PCAF significantly reduced the bone formation both in vitro and in vivo. Mechanistically, PCAF controls BMP signaling genes expression by increasing H3K9 acetylation. Most importantly, PCAF expression is significantly decreased in bone sections of ovariectomized or aged mice. Histone modification enzyme is chemically modifiable; therefore, PCAF may represent a novel therapeutic target for stem cell-mediated regenerative medicine and the treatment of osteoporosis. Stem Cells 2016;34:2332-2341.
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.|National Engineering Lab for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Ping
P
Zhang
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Yunsong
Y
Liu
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Chanyuan
C
Jin
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Min
M
Zhang
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Longwei
L
Lv
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Xiao
X
Zhang
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Hao
H
Liu
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China. kqzhouysh@hsc.pku.edu.cn.|National Engineering Lab for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China. kqzhouysh@hsc.pku.edu.cn.
Yongsheng
Y
Zhou
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010012:Osteogenesis / Q000235:genetics; D010024:Osteoporosis / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D051785:Smad Proteins / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D006657:Histones; D051785:Smad Proteins; D050880:p300-CBP Transcription Factors
Bone morphogenetic protein; H3K9 acetylation; Osteogenic differentiation; Osteoporosis; P300/CBP-associated factor