Retinoic acid-induced Smad3 expression is required for the induction of osteoblastogenesis of mesenchymal stem cells

Instruction of mesenchymal cell fate by the transcription factor C/EBPβ

“…In conjunction with Runx2, C/EBPβ then further drives osteoblast differentiation (Fig. 3) (Dingwall et al, 2011).…”

“…These studies were conducted in mesenchymal chondrogenic cells, representing undifferentiated chondrocytes (Lau et al, 1993;Okazaki et al, 2002). From studies in osteoblasts, we learned that C/EBPβ plays a dual role, as a repressor in undifferentiated MSCs and as a transcriptional activator upon induction of osteoblast differentiation (Dingwall et al, 2011). One could envisage a similar functional change in chondrocytic differentiation, where C/EBPβ may turn from a repressor into an activator once the chondrogenic differentiation program has been initiated.…”

E2F1 impairs all-trans retinoic acid-induced osteogenic differentiation of osteosarcoma via promoting ubiquitination-mediated degradation of RARα

“…14,15 Moreover, ATRA has been found to induce osteoblastic differentiation of mouse and rat mesenchymal stem cells and preosteoblasts. 16,17 All these studies suggest that ATRA can restore normal osteogenesis, and ATRA-based differentiation therapeutics might be feasible for osteosarcoma. However, no clinical applications for ATRA in patients with osteosarcoma have been reported to date.…”

Protein Inhibitor of Activated STAT 1 (PIAS1) Is Identified as the SUMO E3 Ligase of CCAAT/Enhancer-Binding Protein β (C/EBPβ) during Adipogenesis

“…C/EBP␤, a basic leucine zipper (bZIP) transcriptional factor, is involved in many differentiation processes (9)(10)(11)(12). C/EBP␤ plays a role as a major regulator of mesenchymal stem cell fate by acting as an activator of adipogenesis (9,10) and a repressor of osteoblastogenesis (11) and myogenesis (12).…”

“…C/EBP␤ plays a role as a major regulator of mesenchymal stem cell fate by acting as an activator of adipogenesis (9,10) and a repressor of osteoblastogenesis (11) and myogenesis (12). Our previous investigations have shown that C/EBP␤ is rapidly expressed in the 3T3-L1 preadipocyte differentiation program and is maintained at a high level during the early stage of differentiation (6) and that upon sequential phosphorylation by mitogen-activated protein kinase (MAPK), cyclin-dependent kinase 2 (CDK2), and glycogen synthase kinase 3␤ (GSK3␤) (13,14), C/EBP␤ acquires DNA-binding activity, activating the expression of C/EBP␣ and PPAR␥ as well as cell cycle genes essential for mitotic clonal expansion (MCE), a necessary step for terminal adipocyte differentiation (15)(16)(17).…”