Age-related osteoporosis is characterized by the deterioration in bone volume and strength, partly due to the dysfunction of bone marrow mesenchymal stromal/stem cells (MSCs) during aging. Alpha-ketoglutarate (αKG) is an essential intermediate in the tricarboxylic acid (TCA) cycle. Studies have revealed that αKG extends the lifespan of worms and maintains the pluripotency of embryonic stem cells (ESCs). Here, we show that the administration of αKG increases the bone mass of aged mice, attenuates age-related bone loss, and accelerates bone regeneration of aged rodents. αKG ameliorates the senescence-associated (SA) phenotypes of bone marrow MSCs derived from aged mice, as well as promoting their proliferation, colony formation, migration, and osteogenic potential. Mechanistically, αKG decreases the accumulations of H3K9me3 and H3K27me3, and subsequently upregulates BMP signaling and Nanog expression. Collectively, our findings illuminate the role of αKG in rejuvenating MSCs and ameliorating age-related osteoporosis, with a promising therapeutic potential in age-related diseases.
Keyphrases
- bone marrow
- mesenchymal stem cells
- bone regeneration
- bone mineral density
- bone loss
- embryonic stem cells
- stem cells
- umbilical cord
- postmenopausal women
- cell therapy
- mouse model
- high fat diet induced
- metabolic syndrome
- dna methylation
- dna damage
- poor prognosis
- adipose tissue
- wild type
- gene expression
- human health
- binding protein
- single cell
- long non coding rna