A coculture model of synoviocytes and bone for the evaluation of potentialarthritis therapies

Objective: To evaluate the symbiotic relationship between musculoskeletal c ells in the intact joint utilizing a coculture system and to determine if t he model can be utilized to evaluate potential treatments for articular dis eases. Methods: Two neonatal mouse calvariae were placed on steer supports on a mo nolayer of rabbit synovial fibroblasts, and net calcium nux, bone cell acti vity, and undecalcified histology were determined at 6, 24, and 48 h. To de termine if the model was predictive of response to known therapies for arti cular disease, the coculture was incubated in the presence and absence of i ndomethacin or doxycycline, and the net calcium flux was measured. Results: The coincubation of calvariae with synoviocytes led to a fivefold increase in net calcium efflux compared to calvariae alone. The concentrati on in the media of the osteoblastic enzyme alkaline phosphatase increased a t 6 h but decreased thereafter, whereas the concentration of osteoclastic e nzyme beta-glucuronidase increased with time. Undecalcified bone histology revealed progressive demineralization and an increase in the number of oste oclasts in calvariae incubated with synoviocytes compared to calvariae alon e. Both indomethacin and doxycycline inhibited calcium flux from cocultures but the predominant effect of doxycycline was on the synoviocyte whereas t he predominant effect of indomethacin was on bone. Conclusion: The coincubation of synoviocytes with calvariae led to an incre ase in bone mineral dissolution with time. This effect could be partially i nhibited by known treatments for rheumatoid arthritis. Thus, the coculture model may simulate certain aspects of the in vivo processes relevant to rhe umatoid arthritis. This model should prove useful for the study of potentia l therapies for inflammatory arthritis and distinguish between effects of t hese therapies on different cellular components of the joint. (C) 1999 Else vier Science Inc. All rights reserved.