Epigenetic therapy targeting bone marrow mesenchymal stem cells for age-related bone diseases

Abstract

As global aging accelerates, the prevention and treatment of age-related bone diseases are becoming a critical issue. In the process of senescence, bone marrow mesenchymal stem cells (BMSCs) gradually lose the capability of self-renewal and functional differentiation, resulting in impairment of bone tissue regeneration and disorder of bone tissue homeostasis. Alteration in epigenetic modification is an essential factor of BMSC dysfunction during aging. Its transferability and reversibility provide the possibility to combat BMSC aging by reversing age-related modifications. Emerging evidence demonstrates that epigenetic therapy based on aberrant epigenetic modifications could alleviate the senescence and dysfunction of stem cells. This review summarizes potential therapeutic targets for BMSC aging, introduces some potential approaches to alleviating BMSC aging, and analyzes its prospect in the clinical application of age-related bone diseases.

Mechanism of KDM5A‐mediated H3K4me3 modification in the osteogenic differentiation of mesenchymal stem cells in steroid‐induced osteonecrosis of the femoral head

“…30 Notably, the modulation of specific histone modifications can influence DNA methylation patterns and alter the nuclear homeostasis of BMSCs, thereby mitigating BMSCs senescence. 31 In line with these findings, our study revealed that KDM5A, functioning as a histone demethylase, attenuates the osteogenic ability of BMSCs by diminishing H3K4me3 levels and reducing the expression of RUNX2, a pivotal regulatory of osteogenesis, as well as OPN and OCN. 13 loss in rats with osteonecrosis of the femoral head, while its inhibition significantly increased cytotoxicity, cell death, and apoptosis in osteoblasts.…”

“…Additionally, the transplantation of BMSCs into models of femoral head necrosis has been shown to enhance chondrocyte proliferation and partially repair femoral head necrosis 30 . Notably, the modulation of specific histone modifications can influence DNA methylation patterns and alter the nuclear homeostasis of BMSCs, thereby mitigating BMSCs senescence 31 . In line with these findings, our study revealed that KDM5A, functioning as a histone demethylase, attenuates the osteogenic ability of BMSCs by diminishing H3K4me3 levels and reducing the expression of RUNX2, a pivotal regulatory of osteogenesis, as well as OPN and OCN 13 .…”

Targeted cell delivery of mesenchymal stem cell therapy for cardiovascular disease applications: a review of preclinical advancements

“…As investigators begin to translate these and similar preclinical advances into the clinical arena, several important considerations should be taken into account. Modification of MSCs by any strategy should include careful cell phenotypic characterization studies to ensure that innate stem cell properties including multilineage differentiation, self-renewal, and immunodulatory functions are preserved (56,57). Nonbiologic nanocarrier platforms as well as genetic manipulation strategies utilizing viral vectors should be thoroughly interrogated with regards to their toxicity and safety after systemic administration of cell therapeutics (41,(58)(59)(60).…”

Biomimetic Therapeutics for Bone Regeneration: A Perspective on Antiaging Strategies

“…To date, several approaches aimed at combating senescence in bone have been described; from selective elimination of senescent cells (senolytics) [87] to genetic/epigenetic [88,89] approaches or inhibiting the senescence-associated secretory profile (SASP) of senescent cell populations. [90] However, translation of many of these therapies into preclinical animal models is still in its infancy, as in vitro models are still lacking.…”