The interplay between the immune microenvironment and bone aging: From molecular mechanisms to therapeutic interventions
Jianxu Wang, Ying Xin, Zihao Dong, Siying Li, Guang Yang
Abstract
The core mechanism of skeletal aging lies in the comprehensive disruption of microenvironmental homeostasis, involving a multidimensional interactive network comprising immune cells, mesenchymal stem cells, and their differentiated lineages. Although osteoporosis (OP) and osteoarthritis (OA) have traditionally been viewed as distinct degenerative disorders, recent breakthroughs in osteoimmunology reveal their shared immune-aging mechanism: immune cell dysfunction within the bone marrow microenvironment triggers inflammaging, subsequently driving a vicious cycle of bone formation and resorption through the senescence-associated secretory phenotype (SASP). This review not only integrates the molecular landscape of osteoclast-osteoblast-immune triangular crosstalk but also highlights emerging mechanisms such as mitochondrial dysfunction, exosomal communication, and cell death mechanisms, systematically establishing the pivotal role of the immune microenvironment in bone aging and providing a theoretical framework for developing next-generation targeted therapies against skeletal aging.