Integrin αVβ3 as a context-dependent regulator of bone homeostasis: Insights into osteoporosis pathogenesis and therapeutic targeting (Review)

Abstract

Osteoporosis (OP) is a multifactorial skeletal disorder characterized by progressive bone loss, microarchitectural deterioration and an increased risk of fragility fractures resulting from disrupted bone remodeling. Integrin αVβ3 functions as an important regulator of bone homeostasis by coordinating bone cell-extracellular matrix interactions, mechanotransduction and intracellular signaling across multiple bone cell populations. Through context-dependent actions in osteoclasts, osteoblasts, osteocytes, endothelial cells and immune cells, integrin αVβ3 influences osteoclast adhesion and bone resorption, osteoblast differentiation, angiogenesis, inflammatory responses, and estrogen-associated skeletal remodeling. These diverse functions position integrin αVβ3 at the interface of the multiple signaling pathways involved in maintaining bone-metabolic homeostasis. The present review summarizes current evidence regarding the molecular mechanisms underlying the integrin αVβ3-mediated regulation of bone remodeling, discusses the cell-specific and microenvironment-dependent functions of integrin αVβ3 in OP pathogenesis, and critically evaluates the challenges and future directions for translating integrin αVβ3-targeted strategies into clinical applications against OP.