Effects of BMSC-Derived EVs on Bone Metabolism

Abstract

Extracellular vesicles (EVs) are small membrane vesicles that can be secreted by most cells. EVs can be released into the extracellular environment through exocytosis, transporting endogenous cargo (proteins, lipids, RNAs, etc.) to target cells and thereby triggering the release of these biomolecules and participating in various physiological and pathological processes. Among them, EVs derived from bone marrow mesenchymal stem cells (BMSC-EVs) have similar therapeutic effects to BMSCs, including repairing damaged tissues, inhibiting macrophage polarization and promoting angiogenesis. In addition, BMSC-EVs, as efficient and feasible natural nanocarriers for drug delivery, have the advantages of low immunogenicity, no ethical controversy, good stability and easy storage, thus providing a promising therapeutic strategy for many diseases. In particular, BMSC-EVs show great potential in the treatment of bone metabolic diseases. This article reviews the mechanism of BMSC-EVs in bone formation and bone resorption, which provides new insights for future research on therapeutic strategies for bone metabolic diseases.

Application and Molecular Mechanisms of Extracellular Vesicles Derived from Mesenchymal Stem Cells in Osteoporosis

“…Cumulative studies have shown that MSC-EVs can influence downstream signaling cascades by directly translocating their internal cargoes, which in turn regulate bone formation, bone resorption, bone angiogenesis, and immune activity in OP [ 75 , 76 ] (as shown in Figure 2 ). There are many endogenous molecules encapsulated within MSC-EVs.…”

Mesenchymal Stem Cell-Derived Extracellular Vesicles for Bone Defect Repair

“…Among the many cytokines secreted by MSCs, extracellular vesicles (EVs) are nano-phospholipid bilayer vesicles that can be secreted by almost all cells and are formed by “budding” directly from the plasma membrane. According to their diameter, composition, and origin, EVs can be divided into exosomes (Exos), microvesicles, and apoptotic bodies [ 23 ]. Among them, Exos are the most attractive category of EVs.…”

HIF-1α Regulates Bone Homeostasis and Angiogenesis, Participating in the Occurrence of Bone Metabolic Diseases

“…Under physiological conditions, osteoclasts and osteoblasts play a role in maintaining bone resorption and formation in dynamic balance [ 1 ]. Bone marrow mesenchymal stem cells (BMSCs) are important precursor cells of the osteoblast line [ 2 ]. Under appropriate conditions, BMSCs can differentiate into mesenchymal-derived cell types, such as chondrocytes, osteoblasts, and adipocytes, which play a crucial role in bone remodeling [ 3 ].…”

“…Osteoclasts derived from bone marrow-derived macrophages (BMMs) clear old or damaged bone under the trigger of osteocytes while releasing growth factors from the bone matrix, thus inducing BMSCs recruitment and migration to the repair area, resulting in BMSCs differentiation into osteoblasts and formation of new bone at specific sites [ 4 , 5 ]. However, under the pathological conditions of estrogen deficiency, abnormal mechanical stress, and drug side effects, the homeostasis of bone formation and bone resorption is disrupted, leading to osteoporosis, fracture, nonunion, or osteonecrosis of the femoral head [ 2 ]. Therefore, the regulation of bone formation and bone resorption is the basic strategy for preventing and treating bone metabolism-related diseases, in which osteoclasts and osteoblasts play a crucial role.…”