Fibroblast-like Synoviocytes – Actors in Osteoimmunology

Abstract

Rheumatoid arthritis (RA) is an immune mediated inflammatory disease (IMID), characterized by chronic inflammation and irreversible bone loss. Studies have shown that fibroblast-like synoviocytes (FLS), a key cell population in the pathogenesis of RA, have an impact on balancing bone-forming osteoblasts and bone-destroying osteoclasts towards joint damage. Once activated, RA-FLS are able to destroy cartilage and subchondral bone through the release of RANKL, members of the metalloproteinase family and many more cytokines, chemokines and growth factors. Additionally, RA-FLS are responsible for the perpetuation and chronicity of the disease due the interaction with immune cells supporting the influx of T and B lymphocytes, monocytes, macrophages neutrophils and dendritic cells from the blood stream into the inflamed synovial tissue. In this review we highlight the direct and indirect impact of synovial fibroblasts in RA on joint damage and disease progression. Moreover, we describe mechanisms of synovitis and regulators of bone homeostasis in further inflammatory joint diseases such as ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and compare them to RA.

Zusammenfassung

Die rheumatoide Arthritis (RA) ist eine immunvermittelte entzündliche Erkrankung (IMID), die durch chronische Entzündung und irreversiblen Knochenverlust gekennzeichnet ist. Studien haben gezeigt, dass Gelenkfibroblasten eine der Schlüsselrollen im Krankheitsverlauf der RA spielen, indem sie das Gleichgewicht zwischen knochenbildenden Osteoblasten und knochenzerstörenden Osteoklasten beeinflussen. Einmal aktiviert, sind die synovialen Fibroblasten in der Lage, Knorpel und Knochen durch die Freisetzung von RANKL, Mitgliedern der Metalloproteinase-Familie und vielen anderen Zytokinen, Chemokinen und Wachstumsfaktoren zu zerstören. Zudem sind Gelenkfibroblasten für die Perpetuierung und Chronifizierung der Erkrankung verantwortlich, indem sie mit Immunzellen interagieren, um den Einstrom von T- und B-Lymphozyten, Monozyten, Makrophagen, Neutrophilen und dendritischen Zellen aus der Blutbahn in das entzündete Synovialgewebe fördern. In dieser Übersichtsarbeit stellen wir den direkten und indirekten Einfluss der synovialen Fibroblasten bei RA auf die Gelenkschädigung und das Fortschreiten der Erkrankung dar. Darüber hinaus beschreiben wir Mechanismen der Synovitis und Regulatoren der Knochenhomöostase bei anderen entzündlichen Gelenkerkrankungen wie die ankylosierende Spondylitis (AS) und die Psoriasis-Arthritis (PsA) und vergleichen sie schließlich mit RA.

Key words

osteoimmunology - bone remodelling - fibroblast-like synoviocytes - RA

Schlüsselwörter

Osteoimmunologie - Knochenhomöostase - synoviale Fibroblasten - RA

^* shared first authors

Publication History

Received: 22 July 2021

Accepted: 04 October 2021

Article published online:
18 November 2021

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