Monocyte-derived fibrocytes contribute to nucleus pulposus fibrosis and intervertebral disc degeneration

Abstract

AbstractNucleus pulposus (NP) undergoes fibrosis, leading to structural and mechanical anomalies of intervertebral discs that prone to degeneration. Fibroblastic cells emerge and account for NP fibrosis, yet their nature and origin remain elusive. Degenerative NP cells are highly heterogenous and may contain immune cells. By meta-analysis of single-cell data, we here showed an enrichment of hematopoietic fibrocyte-like cells, defined by CD45 and collagen I dual positivity, in human NP specimens which increases with degeneration severity. We identified fibrocytes subtypes with a myofibroblast differentiation capacity in NP fibrosis. These fibrocytes were recruited in NP fibrosis mediated by injury-induced mouse disc degeneration. Monocyte depletion in CD11b-DTR mice attenuated NP fibrosis and myofibroblast generation, and prevented disc height loss and histomorphological abnormalities. Our findings suggest that fibrocyte-like cells may mediate NP fibrosis and therefore be a potential target for modifying disc degeneration and promoting its repair.