The Role of Senescence-Associated Secretory Phenotype in Bone Loss

Abstract

As the population of most nations have a large proportion of older individuals, there is an increase in the prevalence of osteoporosis. Consequently, scientists have focused their attention on the pathogenic mechanisms of osteoporosis. Owing to an increase in studies on cellular senescence in recent years, research has begun to focus on the function of the senescent microenvironment in osteoporosis. With chronic inflammation, senescent cells in the bone marrow secrete a series of factors known as senescence-associated secretory phenotype (SASP) factors, acting on their own or surrounding healthy cells and consequently exacerbating ageing.The components of the SASP may differ depending on the cause of osteoporosis. This review aimed to summarize the relationship between SASP factors and osteoporosis and suggest new insights into the mechanistic investigation of osteoporosis.

Keywords: bone loss; osteoporosis; senescence; senescence-associated secretory phenotype (SASP); stem cell.

FIGURE 1

When cells are senescence induced by external stimulation, SASP can be released to aggravate their own senescence or induce the senescence of surrounding normal cells. For (A), under the influence of radiation, BMSCs become senescent, causing activation of the JAK1/STAT3 pathway and release of SASP (e.g., IL-6, IL-8, MMP9) to reduce the osteogenic differentiation ability of osteoblasts. (B) When MLO-Y4 cells were irradiated, MLO-Y4 was induced to senesce, which in turn released SASP (e.g,. IL-1α, IL-6, MMP-3, IGFBP-6, etc.) thus affecting the normal growth of BMSC and reducing their osteogenic differentiation ability and adipogenic differentiation ability. In (C), human adipose MSCs were induced to undergo senescence by radiation, and the released SASP could inhibit MC3T3 osteogenic differentiation, and the process could be alleviated by JAK inhibitors. (D–F), LPS acting on osteoblasts induced senescence and thus inhibited osteogenic differentiation of osteoblasts; when LPS and SCM (senescence conditioned medium) were combined to act on osteoblasts, the osteogenic differentiation and migration ability of osteoblasts were greatly reduced, and this process could be alleviated by P38-MAPK inhibitor. Abbreviations: SCM, senescence-conditioned mediators, LPS, Lipopolysaccharide.