Cellular and molecular changes in the human osteoarthritic and aging hip pulvinar

Abstract

AbstractOsteoarthritis (OA) represents a multifaceted pathology characterized by intricate signaling across various joint tissues, where the sub-synovial adipose tissue (ssAT) has been suggested to play diverse roles, from serving as a stem cell reservoir, mechanosensing, serving as a neuroendocrine organ, to modulating inflammation. In this study, we aimed to uncouple the cellular and molecular alterations within the human hip ssAT (the pulvinar) linked to OA and aging, elucidating the distinct contributions of disease onset and progression versus normal aging. Our findings show a pronounced increase in mesenchymal stem/progenitor cells (MSPCs) in the osteoarthritic pulvinar, associated with the upregulation of putative MSPC markers (DPP4, and THY1), indicating an adaptive repair response. Concurrently, in OA patients we observed an altered immune landscape featuring reduced innate immune cells and elevated exhausted CD8+ cells, along with upregulation of genes critical for inflammation and fibroblast activation. Our findings reveal a nuanced picture of OA, where increased stem cell numbers and vascularization, combined with specific gene expression patterns differentiate OA from normal aging. This study not only delineates the roles of inflammation, immune regulation, and stem cell activity in the OA pulvinar but also identifies potential therapeutic targets to modulate these pathways, offering novel insights into OA as a complex interplay of degenerative and intrinsic tissue repair.