Synovium from Arthritic Equine Joints Develops A Latent Osteogenic Phenotype

Introduction: Enthesophytes, periarticular ossification and ankylosis are characteristics of arthritic joints. This study was carried to determine whether synovium from arthritic joints has osteogenic capacity not evident in normal synovium.

Materials and Methods: This study was conducted in a manner consistent with the U.S. NIH guidelines. Synovium from clinically arthritic and matched normal joints from adult horses was digested in collagenase. Isolated cells were expanded though two passages or subject to primary synoviocyte osteogenic analyses. Cells were maintained in control medium, in standard osteogenic medium or in osteogenic medium with BMP-2 for up to 14 days. Osteogenesis was assessed by osteogenic gene induction, ALP activity, and Alizarin Red staining. Quantitative outcomes were analyzed by ANOVA (p < 0.05).

Results: Normal primary synovial cells showed minimal osteogenic capacity. In contrast, primary arthritic synovial cells upregulated ALP expression and activity; responses increased by BMP-2. There was little or no Alizarin Red stain uptake in normal synoviocyte osteogenic cultures. Focal staining was present in arthritic synoviocyte cultures. BMP-2 stimulated intense staining of aggregates in arthritic synoviocyte cultures only. Resting and inducible expression of Runx2 and OSX were consistently increased in arthritic synovial cell cultures. Passage 3 arthritic synovial cells were more osteogenic than primary cells. In contrast, in vitro expansion had little effect on osteogenesis of normal cells.

Discussion/Conclusion: These results show that synovium from arthritic joints has osteogenic capacity not evident in normal synovium and provides an explanation for the origin of periarticular bone formation in arthritic joints.

Acknowledgment: Funded by USDA Hatch and VOS.