Bidirectional regulation of osteogenic differentiation by the FOXO subfamily of Forkhead transcription factors in mammalian MSCs

AbstractThrough loss ‐ and gain‐of‐function experiments in knockout and transgenic mice, Forkhead box O (FOXO) family transcription factors have been demonstrated to play essential roles in many biological processes, including cellular proliferation, apoptosis and differentiation. Osteogenic differentiation from m esenchymal stem cells (MSCs) into osteoblasts is a well‐organized process that is carefully guided and characterized by various factors, such as runt‐related transcription factor 2 (Runx2), β‐catenin, osteocalcin (OCN), alkaline phosphatase (ALP) and activating transcription factor 4 (ATF4). Accumulating evidence suggests multiple interactions among FOXO members and the differentiation regulatory factors listed above, resulting in an enhancement or inhibition of osteogenesis in different stages of osteogenic differentiation. To systematically and integrally understand the role of FOXOs in osteogenic differentiation and explain the contrary phenomena observed in vitro and in vivo, we herein summarized FOXO‐interacting differentiation regulatory genes/factors and following alterations in differentiation. The underlying mechanism was further discussed on the basis of binding types, sites, phases and the consequent downstream transcriptional alterations of interactions among FOXOs and differentiation regulatory factors. Interestingly, a bidirectional effect of FOXOs on balancing osteogenic differentiation was discovered in MSCs. Moreover, FOXO factors are...
Source: Cell Proliferation - Category: Cytology Authors: Tags: REVIEW ARTICLE Source Type: research