The BRIC-GARN Meeting 2011: of mice and men

the Hilton Tokyo Bay from 14 to 16 November 2011. Th e hotel is a short distance from Tokyo Disneyland and, for most guests, the mice were of the cartoon variety that descended from Steamboat Willie. Now known as Mickey Mouse, Steamboat Willie was the brilliant product of Walt Disney’s imagination. Not surprisingly, more than a few children cavorting in the hotel lobby wore the iconic black ears as treasured souvenirs of their trip to the Magic Kingdom. Th e other Hilton guests thinking about mice were attending the BRIC–GARN Meeting 2011. Th is outstanding international congress, organized by Professor Kusuki Nishioka, Director and Chairman, Institute of Medical Science, Tokyo, encompassed both the Bio-Rheumatology International Congress (BRIC) and the ninth Global Arthritis Research Network (GARN) meeting. Th e GARN meeting brings together investigators from around the world to discuss the pathogenesis and treatment of infl ammatory arthritis. For these people, the mice uppermost in the mind were of the knockout and transgenic kind. Indeed, one of the highlights of the meeting was a presentation on slickly engineered rodents whose cells glowed neon-bright to track the peregrinations of an overexpressed fl uorescent protein construct. Among tissues featured at the meeting, bone received signifi cant attention – especially with regard to the interface with the immune system. Indeed, bone – often viewed as an inert, albeit durable and hard, scaff old for the body construction – is intensively dynamic as osteoclasts and osteoblasts engage in relentless surface remodel ing. In this lively cellular pas de deux, RANK– RANKL interactions are at the center of action. As therapies targeting RANKL enter practice, questions will abound on the conse quences of its inhibition, not only for the bone itself but for the immune cells that also utilize this system. Indeed, as described by Professor Yongwon Choi from University of Pennsylvania in his study on a molecule called OSCAR, osteoclasts and osteoclasts have many similari ties to T cells and antigen-presenting cells; bone cells are homebodies, however, whereas immune cells are wanderers. Another cell in the spotlight at the meeting was the fi broblast. As shown in studies by Professor Steff en Gay from Zurich, synovial fi broblasts play a key role in the pathogenesis of rheumatoid arthritis (RA), with an invasive and destructive phenotype bearing the hallmark of epigenetic modifi cation. Th e driving force of such modifi cation is not known but the presence of aberrant base methylation suggests that pathogenesis involves changes to the DNA at the cellular level. As such, agents that undo epigenetic modifi cation could have therapeutic benefi t by reconfi guring genes and returning the fi broblasts to a more subdued and tractable state. Intriguingly, one compound that has potential as an epigenetic modifi er is S-adenosyl methionine. Called SAME (pronounced Sammy), this agent has long had popularity as an alternative therapy for RA and was touted on American television by the actor James Coburn of Our Man Flint fame. Coburn himself had severe RA. Imagine the irony if SAME turned out to be the real deal. Professor Gay also highlighted the importance of miRNA in the regulation of fi broblast biology. miRNA is hot right now and the role of these regulatory nucleic acids was reprised in presentations by Professor Iain McInnnes from Glasgow and Professor Nan Shen from Shanghai. Many studies in the future will no doubt investigate miRNA signatures as biomarkers comparable with mRNA signatures. Th e potential of miRNAs as targets of therapy remains to be tested, however, with such approaches possibly encountering the same obstacles as did antisense; the delivery of nucleic acids inside cells can be a challenge to say the least. Th us far, synovial fi broblasts have not been put directly in the cross-hairs of a targeted therapy, although undoubtedly many current agents can aff ect the function of these cells by reducing the activity of other interacting cell types and their production of mediators. A study by Professor Ulf Muller-Ladner from Giessen raised the intriguing possibility that synovial fi broblasts can migrate from joint to joint, in essence causing synovitis to metastasize. Th ese experiments were performed in a SCID mouse model in which synovial tissue and cartilage from a patient are implanted into the mouse and cell migration is tracked by © 2010 BioMed Central Ltd The BRIC–GARN Meeting 2011: of mice and men