Research Progress on the Regulation Mechanism of Senescence-associated Secretory Phenotype in Osteoporosis

Abstract

Senescence-associated secretory phenotype (SASP) is an important feature of cellular senescence and plays an important role in regulating the disease microenvironment. At present, the role of SASP in intervening bone metabolism and inducing bone loss is very limited. Therefore, this paper discusses the regulatory mechanism of SASP in osteoporosis models and summarizes its regulatory characteristics: SASP is fully expressed in senescent bone cells and transmits aging effects to mesenchymal stem cells in an autocrine/paracrine manner, thereby interfering with osteogenic differentiation. SASP activates immune cells and promotes their aging, thus inducing the formation of inflammatory tissue microenvironment and aggravating bone loss. Mitochondrial homeostasis, pathologic hyperglycemia, and obesity-induced fat accumulation all promote SASP expression, thus disrupting microenvironmental homeostasis and transmitting aging effects to bone tissue. To sum up, understanding the role of SASP in osteoporosis lays a solid foundation for us to develop anti-SASP therapy for osteoporosis in the future.

Keywords

• osteoporosis|senescence-associated secretory phenotype|cell senescence|metabolic disorders|immunomodulation