A coculture model of synoviocytes and bone for the evaluation of potential arthritis therapies.
OBJECTIVE
To evaluate the symbiotic relationship between musculoskeletal cells in the intact joint utilizing a coculture system and to determine if the model can be utilized to evaluate potential treatments for articular diseases.


METHODS
Two neonatal mouse calvariae were placed on steel supports on a monolayer of rabbit synovial fibroblasts, and net calcium flux, bone cell activity, and undecalcified histology were determined at 6, 24, and 48 h. To determine if the model was predictive of response to known therapies for articular disease, the coculture was incubated in the presence and absence of indomethacin 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 concentration in the media of the osteoblastic enzyme alkaline phosphatase increased at 6 h but decreased thereafter, whereas the concentration of osteoclastic enzyme beta-glucuronidase increased with time. Undecalcified bone histology revealed progressive demineralization and an increase in the number of osteoclasts in calvariae incubated with synoviocytes compared to calvariae alone. Both indomethacin and doxycycline inhibited calcium flux from cocultures but the predominant effect of doxycycline was on the synoviocyte whereas the predominant effect of indomethacin was on bone.


CONCLUSIONS
The coincubation of synoviocytes with calvariae led to an increase in bone mineral dissolution with time. This effect could be partially inhibited by known treatments for rheumatoid arthritis. Thus, the coculture model may simulate certain aspects of the in vivo processes relevant to rheumatoid arthritis. This model should prove useful for the study of potential therapies for inflammatory arthritis and distinguish between effects of these therapies on different cellular components of the joint.
Moe
S M
SM
Department of Medicine, Indiana University Medical Center, Wishard Memorial Hospital, Indianapolis 46202, USA. smoe@iupui.edu
Bailey
A M
AM
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D000831:Animals, Newborn; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry; D004318:Doxycycline / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005966:Glucuronidase / Q000032:analysis; D007213:Indomethacin / Q000494:pharmacology*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D012886:Skull / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D017077:Culture Media, Conditioned; D000469:Alkaline Phosphatase; D005966:Glucuronidase; D004318:Doxycycline; D002118:Calcium; D007213:Indomethacin