Int J Oral Biol.  2024 Sep;49(3):69-78. 10.11620/IJOB.2024.49.3.69.

Decline in sestrin 2 expression during aging shifts mesenchymal stem cell differentiation from osteogenic to adipogenic lineage

• Kim DY
• Park HJ
• Baek JH

• KMID: 2562649
• DOI: http://doi.org/10.11620/IJOB.2024.49.3.69

Abstract

Sestrin 2 (SESN2) is a member of the sestrin family of stress-induced proteins that negatively regulate agingassociated biological processes. This study aims to investigate the role of SESN2 in regulating the differentiation potential and senescence of mesenchymal stem cells (MSCs) derived from young and elderly donors. Bulk RNA sequencing revealed a common decline in the SESN2 mRNA levels in MSCs from elderly individuals, which was confirmed via reverse transcription-polymerase chain reaction and western blot analyses. SESN2 knockdown in MSCs from young donors resulted in phenotypic changes similar to those in MSCs from elderly donors, including an enhanced expression of senescence and adipogenic markers and diminished expression of osteogenic markers. To confirm the effect of decreased SESN2 expression on osteogenic and adipogenic differentiation, we induced Sesn2 knockdown in mouse bone marrow-derived MSCs. Sesn2 knockdown suppressed the mRNA expression of osteogenic marker genes, alkaline phosphatase activity, and matrix mineralization. Furthermore, Sesn2 knockdown enhanced mRNA expression of the adipogenic marker genes and intracellular lipid accumulation. These results suggest that a decline in SESN2 expression during aging contributes to the shift of MSC differentiation from osteogenic to adipogenic lineage.

Keyword

Sestrin 2; Aging; Osteoblasts; Adipocytes; Mesenchymal stem cells