Primary cilia in fibroblast-like type B synoviocytes lie within a cilium pit: a site of endocytosis

The synovium is a thin connective tissue that lines the joint space of free moving articulations. In this report, the expression, structure, and composition of non-motile (primary) cilia in fibroblast-like synoviocytes (FLS) that populate the synovium have been studied. Primary cilia are non-motile, microtubule-based organelles that have been found in a variety of vertebrate cell types. We document that primary cilia are expressed in normal human synovium FLS, cultured human FLS, and FLS cells present in human synovial fluid, and that the cellular region occupied by the primary cilium shows a similar and highly defined architecture within these FLS. This architecture includes the presence of a unique structure that surrounds the lower portion of the cilium shaft. This structure, given the term cilium-pit, includes a space, the pit reservoir. Actin filament bundles surround the cilium-pit, and when these bundles are removed experimentally the volume of the cilium-pit and its continuity with the extracellular environment changes. Finally, this study documents that the cilium-pit is a site of endocytosis and is also the site for the localization of receptors (TNF receptors TNFR1 and TNFR2) associated with synoviocyte function. Taken together, the results of the present study suggest that the FLS cilium-pit functions to regulate the exposure of the primary cilium, both spatially and temporally to extracellular molecules and to couple primary cilium based signaling pathways with those linked to endocytosis.