Influence of pathological microenvironments on mesenchymal stem/stromal cell fate: role of long non-coding RNAs in bone-related diseases

The bidirectional relationship between pathological microenvironments and mesenchymal stem/stromal cells (MSCs) is known as a pivotal factor influencing the progression of bone-related disease and therapeutic outcomes. MSCs, characterized by their remarkable plasticity and excellent immunomodulatory abilities, play central roles in various physiological and pathological processes, especially in bone regeneration and repair. Under pathological conditions, such as osteoarthritis, osteoporosis, or bone tumors, the tissue microenvironment can significantly alter MSC behavior, leading to impaired differentiation, dysregulated immune responses, or abnormal tissue remodeling. This dynamic relationship is regulated by diverse molecular signals, where long non-coding RNAs (lncRNAs) emerge as critical regulators of MSC biology. LncRNAs influence MSC differentiation, immunomodulatory functions, and responses to microenvironmental cues through diverse molecular mechanisms. The systematic review elucidates the roles of various lncRNAs involved in different aspects of MSC biology under pathological conditions and their potential as therapeutic targets or biomarkers for bone-related disorders.