期刊
EXPERIMENTAL GERONTOLOGY
卷 148, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2021.111313
关键词
Aging; Osteoporosis; MSC senescence; Bmi-1; IL-1?
资金
- National Natural Science Foundation of China [81660376, 82060266]
- Youth Science and Technology Talents Development Project of Guizhou Provincial Department of Education [[2016]194]
Osteoporosis is more prevalent as individuals age due to bone marrow mesenchymal stem cells (MSCs) undergoing senescence, resulting in reduced bone formation and repair. Studies showed that MSCs from aged mice exhibited senescent phenotypes with decreased Bmi-1 expression and increased IL-1β levels in the bone marrow microenvironment, leading to MSC senescence.
Osteoporosis is becoming increasingly prevalent with individual aging. Recent studies found that bone marrow mesenchymal stem cells (MSCs) undergo senescence along with the progression of age-related osteoporosis, leading to a decreased rate of new bone formation and fracture repair. The underlying mechanism of MSC senescence in the aged bone marrow has not been clarified yet. Here we found that MSCs from aged mice (12month-old, O-MSCs) exhibited apparent senescent phenotypes compared with those from young controls (2month-old, Y-MSCs), including lower proliferation rate, impaired self-renewal capacity, increased p16Ink4a expression and shifted differentiation balance to favor adipocytes over osteoblasts. Bmi-1, one of the main factors that regulate stem cell self-renewal, is dramatically decreased in O-MSCs. Knocking-down of Bmi-1 in Y-MSCs lead to cellular senescence, while over-expression of it rejuvenated O-MSCs. We further showed that the level of IL-1? is much higher in the bone marrow fluid of aged mice, which significantly inhibited Bmi-1 expression in MSCs. Our present study indicated that IL-1?, a key component of the senescence-associated secretory phenotype (SASP), is elevated in the aged bone marrow microenvironment, leading to decreased Bmi-1 expression in MSCs and consequently, MSC senescence.
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