Single-cell RNA sequencing of the meniscus: insights into cellular heterogeneity and therapeutic targets

PURPOSE: As a key component of the knee joint, meniscal health and function directly influence joint stability and the progression of degenerative conditions such as osteoarthritis. Single-cell RNA sequencing has been increasingly applied in meniscus research, providing new insights into tissue complexity and intercellular interactions. This review summarizes recent advances in single-cell RNA sequencing and its applications in meniscus research. METHODS: Relevant literature was reviewed and synthesized, with a focus on cell type identification, subpopulation heterogeneity, disease pathogenesis, and potential therapeutic targets. RESULTS: The findings indicate that single-cell RNA sequencing can elucidate the critical roles of specific meniscal cell clusters in maintaining tissue homeostasis, mediating degenerative processes, and facilitating injury repair, thereby providing a foundation for early diagnosis, targeted interventions, and tissue engineering strategies. Nevertheless, several challenges still hinder the clinical translation of single-cell RNA sequencing findings, including the dense extracellular matrix of the meniscus, difficulties in cell dissociation, limited cell viability and yield, cross-species differences, inconsistent analytical workflows, high sequencing costs, and the loss of spatial information. CONCLUSIONS: Integration of single-cell RNA sequencing with spatial transcriptomics, multi-omics approaches, and analyses of the meniscus and adjacent joint tissues may help identify disease-related biomarkers, support patient stratification, guide targeted interventions, and advance tissue engineering and regenerative medicine strategies for meniscus degeneration and osteoarthritis.