Abstract
A significant macrophage and T-cell infiltrate commonly occurs in inflammatory joint conditions such as rheumatoid arthritis that have significant bone destruction. Cytokines produced by activated macrophages and T cells are implicated in arthritis pathogenesis and are involved in osteoclast-mediated bone resorption. The scope of the present review is to analyze current knowledge and to provide a better understanding of how macrophage-derived factors promote the differentiation of a novel T-helper subset (Th17) that promotes osteoclast formation and activation.
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory disease driven by immune dysregulation
We provide a brief overview of four T-cell subsets and the factors that drive their differentiation into these subsets, and we concentrate on how the signature cytokine(s) of these T cells impact inflammationdriven osteoclastogenesis in arthritis
Th17 cells are a newly discovered T-cell lineage that plays a role in the adaptive immune response to extracellular pathogens
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease driven by immune dysregulation. IL-17A induces RANKL expression by synovial fibroblasts and osteoblasts to indirectly drive bone erosion [60] and to activate synovial macrophages to secrete the known osteoclastogenic factors TNF and IL-1β [61]. Exogenous IL-4 addition to the CIA model had minimal impact on the outward signs of inflammation, but showed a bone-preserving biology including decreased bone erosion, tartrate-resistant acid phosphatase activity, and RANKL message [86,87] These data do not support that Th2 cells or their signature cytokines IL-4 and IL-13 are major drivers of inflammation-associated osteoclastogenesis, but instead support that this lineage along with the Th1 lineage may counteract Th17 products and other pro-osteoclast inflammation factors present in the RA joint. This same concept holds true from an osteoclastogenesis viewpoint since master differentiation factors and signature cytokines of the Th1, Th2, and Treg lineage inhibit osteoclastogenesis and Th17 products stimulate osteoclastogenesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
