Fibrocyte: A missing piece in the pathogenesis of fibrous epulis

Objectives: To explore the role of fibrocytes in the recurrence and calcification of fibrous epulides. Methods: Different subtypes of fibrous epulides and normal gingival tissue specimens were first collected for histological and immunofluorescence analyses to see if fibrocytes were present and whether they differentiated into myofibroblasts and osteoblasts upon stimulated by transforming growth factor-β1 (TGF-β1). Electron microscopy and elemental analysis were used to characterize the extracellular microenvironment in different subtypes of fibrous epulides. Human peripheral blood mononuclear cells (PBMCs) were subsequently isolated from in vitro models to mimic the microenvironment in fibrous epulides to identify whether TGF-β1 as well as the calcium and phosphorus ion concentration in the extracellular matrix (ECM) of a fibrous epulis trigger fibrocyte differentiation. Results: Fibrous epulides contain fibrocytes that accumulate in the local inflammatory environment and have the ability to differentiate into myofibroblasts or osteoblasts. TGF-β1 promotes fibrocytes differentiation into myofibroblasts in a concentration-dependent manner, while TGF-β1 stimulates the fibrocytes to differentiate into osteoblasts when combined with a high calcium and phosphorus environment. Conclusions: Our study revealed fibrocytes play an important role in the fibrogenesis and osteogenesis in fibrous epulis, and might serve as a therapeutic target for the inhibition of recurrence of fibrous epulides.