Local delivery of tetramethylpyrazine eliminates the senescent phenotype of bone marrow mesenchymal stromal cells and creates an anti-inflammatory and angiogenic environment in aging mice

Aging Cell
Bo GaoLiu Yang

Abstract

Aging drives the accumulation of senescent cells (SnCs) including stem/progenitor cells in bone marrow, which contributes to aging-related bone degenerative pathologies. Local elimination of SnCs has been shown as potential treatment for degenerative diseases. As LepR+ mesenchymal stem/progenitor cells (MSPCs) in bone marrow are the major population for forming bone/cartilage and maintaining HSCs niche, whether local elimination of senescent LepR+ MSPCs delays aging-related pathologies and improves local microenvironment need to be well defined. In this study, we performed local delivery of tetramethylpyrazine (TMP) in bone marrow of aging mice, which previously showed to be used for the prevention and treatment of glucocorticoid-induced osteoporosis (GIOP). We found the increased accumulation of senescent LepR+ MSPCs in bone marrow of aging mice, and TMP significantly inhibited the cell senescent phenotype via modulating Ezh2-H3k27me3. Most importantly, local delivery of TMP improved bone marrow microenvironment and maintained bone homeostasis in aging mice by increasing metabolic and anti-inflammatory responses, inducing H-type vessel formation, and maintaining HSCs niche. These findings provide evidence on the mechanisms, ch...Continue Reading

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Citations

Aug 28, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Junyu ChenAnjali P Kusumbe
Sep 6, 2018·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Bombi LeeDae-Hyun Hahm
Jul 10, 2019·Stem Cells International·Vasilis Paspaliaris, George Kolios
Jun 26, 2020·Frontiers in Cell and Developmental Biology·Xueke ZhouXin Li
Jan 18, 2020·International Journal of Molecular Sciences·Abdul QadirAirong Qian
Oct 27, 2020·Stem Cells International·Provvidenza M AbruzzoCarlo Ventura
Apr 6, 2021·Current Molecular Biology Reports·Yajun Liu, Qian Chen
Sep 26, 2019·Gerontology·Magdalena Hagen, Emmanuel Derudder

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Methods Mentioned

BETA
ubiquitination
ELISA
flow cytometry
immunoprecipitation
PCR
ChIP
reverse transcription PCR

Software Mentioned

CellQuest
sas

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