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.
Highlights
We mainly focus on epigenetic marks and modifiers in regulating Mesenchymal Stem Cells (MSCs) aging in vivo or in vitro, in order to clarify the interactive link between epigenetic regulation and aging-related tissue diseases such as osteoporosis, and offer some clues for future utilization of epigenetics mediated tissue regeneration [15]
Epigenetic regulation of MSCs occurs in several steps of transcription, including chromatin remodeling, DNA methylation, and histone modification, and posttranscription, including mRNA processing and noncoding RNAs (ncRNAs) regulation
Epigenetic markers and modifiers have been proved to play indispensable roles in MSC aging and fundamental homeostasis in vivo, both of which are related to the pathogenesis of tissue disorders in aging and diseases
Summary
Apart from the aforementioned two basic characteristics, MSCs exhibit various positive effects through paracrine action and immunomodulation during tissue repair, including regulating angiogenesis and osteoclastogenesis and guiding immune communication [7,8,9] These properties signify that MSCs could perform extensive and active interactions with tissuespecific stem cell niches and represent an ideal and promising tool for tissue regeneration. Therein, biased differentiation can be induced by the imbalance between runt-related transcription factor 2 (Runx2) and peroxisome proliferator-activated receptor γ (PPARγ) pathway These changes during senescence underlie bone mass loss and fat accumulation in aged or diseased skeletal tissues [10,11,12,13]. Further rationalizing and understanding the function mechanism of different epigenetic marks and modifiers occurring in MSC aging are of instructive importance to analyze the pathogenesis of aged and diseased tissue disorders and explore more effective therapeutic or regenerative strategies
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