Fas receptor induces apoptosis of synovial bone and cartilage progenitor populations and promotes bone loss in antigen‐induced arthritis

Abstract

ABSTRACT Rheumatoid arthritis (RA) is an inflammatory joint disease that eventually leads to permanent bone and cartilage destruction. Fas has already been established as the regulator of inflammation in RA, but its role in bone formation under arthritic conditions is not completely defined. The aim of this study was to assess the effect of Fas inactivation on the bone damage during murine antigen‐induced arthritis. Subchondral bone of wild‐type (WT) and Fas‐knockout (Fas −/− ) mice was evaluated by histomorphometry and microcomputerized tomography. Proportions of synovial bone and cartilage progenitors were assessed by flow cytometry. Synovial bone and cartilage progenitors were purified by fluorescence‐activated cell sorting and expression of Fas and Fas‐induced apoptosis were analyzed in vitro . Results showed that Fas −/− mice developed attenuated arthritis characterized by preserved epiphyseal bone and cartilage. A proportion of the earliest CD200 + bone and cartilage progenitors was reduced in WT mice with arthritis and was unaltered in Fas −/− mice. During osteoblastic differentiation in vitro , CD200 + cells express the highest levels of Fas and are removed by Fas ligation. These results suggest that Fas‐induced apoptosis of early CD200 + osteoprogenitor population represents potential mechanism underlying the impaired bone formation in arthritis, so their preservation may represent the bone‐protective mechanism during arthritis.—Lazić Mosler, E., Lukač, N., Flegar, D., Fadljević, M., Radanović, I., Cvija, H., Kelava, T., Ivčević, S., Šućur, A., Markotić, A., Katavić, V., Marušić, A., Grčević, D., Kovačić, N. Fas receptor induces apoptosis of synovial bone and cartilage progenitor populations and promotes bone loss in antigen‐induced arthritis. FASEB J. 33, 3330–3342 (2019). www.fasebj.org