Deciphering the Acetabular Labrum's Cellular Atlas: MDK Inhibition as a Novel Therapeutic Method for Developmental Dysplasia of the Hip

Abstract

DDH is far more than just a contributing factor to hip osteoarthritis; it represents a formidable challenge to the health of infants and young children. While historical research has largely focused on the osseous abnormalities associated with DDH, current surgical interventions, though prevalent, often carry significant and unavoidable side effects. To break through these limitations, the study delved into the acetabular labrum, a crucial intra-articular structure that presents abnormalities in DDH patients. Through single-cell combined spatial transcriptomic analysis of the acetabular labrum under diverse conditions, a comprehensive examination of the changes of DDH tissue changes at the single-cell level is pioneered, conclusively linking aberrant fibrocartilage stem/progenitor cell proliferation to disease progression. The subsequent in vivo and in vitro experiments unequivocally identify the MK signaling pathway as a pivotal target for DDH treatment. Localized administration of its specific inhibitor not only substantially alleviates early structural abnormalities in DDH but also lays a robust and promising foundation for the innovation and clinical translation of new therapeutic strategies for DDH. In summary, the findings not only deepen the understanding of DDH pathogenesis but also pave the way for innovative therapeutic strategies that prioritize both efficacy and safety.