Oxytocin/oxytocin receptor signaling in mesenchymal stem cell differentiation: current evidence and future perspectives on osteogenesis, adipogenesis, and chondrogenesis

Mesenchymal stem cells (MSCs) have emerged as promising therapeutic tools for musculoskeletal regenerative medicine because of their multilineage differentiation capacity, immunomodulatory properties, and paracrine-mediated tissue repair effects. However, the therapeutic efficacy of MSC-based approaches is often limited by impaired cellular function caused by aging, chronic inflammation, oxidative stress, and disease-associated microenvironments. Consequently, increasing attention has focused on strategies to enhance MSC function and optimize their regenerative capacity. Oxytocin (OXT), a neuroendocrine peptide classically recognized for its roles in reproduction and social behavior, has recently emerged as a multifunctional regulator involved in peripheral tissue homeostasis and regeneration. Growing evidence suggests that OXT/OXT receptor signaling influences MSC biology by regulating lineage commitment, cellular stress responses, and reparative potential. In this mini review, we summarize current evidence regarding the effects of OXT on MSC differentiation, with particular emphasis on osteogenesis, adipogenesis, and chondrogenesis in the context of musculoskeletal regeneration. Furthermore, we discuss the translational potential of OXT/OXT receptor signaling, including MSC priming strategies, biomaterial-assisted OXT delivery, and future application of synovial MSC-based therapies for cartilage repair. Finally, we highlight current knowledge gaps and future perspectives regarding OXT as a novel biological modulator for enhancing MSC-based musculoskeletal regenerative therapies.