Epigenetic Regulation in Mesenchymal Stem Cell Aging and Differentiation and Osteoporosis

Abstract

Mesenchymal stem cells (MSCs) are a reliable source for cell-based regenerative medicine owing to their multipotency and biological functions. However, aging-induced systemic homeostasis disorders in vivo and cell culture passaging in vitro induce a functional decline of MSCs, switching MSCs to a senescent status with impaired self-renewal capacity and biased differentiation tendency. MSC functional decline accounts for the pathogenesis of many diseases and, more importantly, limits the large-scale applications of MSCs in regenerative medicine. Growing evidence implies that epigenetic mechanisms are a critical regulator of the differentiation programs for cell fate and are subject to changes during aging. Thus, we here review epigenetic dysregulations that contribute to MSC aging and osteoporosis. Comprehending detailed epigenetic mechanisms could provide us with a novel horizon for dissecting MSC-related pathogenesis and further optimizing MSC-mediated regenerative therapies.

Figure 1

Factors in epigenetic regulation. Epigenetic regulation occurs in several steps of transcription (such as chromatin remodeling, DNA methylation, and histone modification) and posttranscription (such as mRNA processing and ncRNA regulation). Specific regulatory factors participate in each process.

Figure 2

Application of epigenetic regulation in (a) skeletal diseases and (b) bone regeneration. Exogenous blocking or supplement and direct gene manipulation are separately used in both conditions.