Bone and Joint Institute
Global Deletion of Pannexin 3 Resulting in Accelerated Development of Aging-Induced Osteoarthritis in Mice
Document Type
Article
Publication Date
7-1-2021
Journal
Arthritis and Rheumatology
Volume
73
Issue
7
First Page
1178
Last Page
1188
URL with Digital Object Identifier
10.1002/art.41651
Abstract
Objective: Osteoarthritis (OA) results in pathologic changes in the joint tissue. The mechanisms driving disease progression remain largely unclear, and thus disease-modifying treatments are lacking. Pannexin 3 (Panx3) was identified as a potential mediator of cartilage degeneration in OA, and our previous study in mice indicated that deletion of the Panx3 gene delayed surgically induced cartilage degeneration. This study was undertaken to examine the role of Panx3 in other OA subtypes, particularly primary OA during aging, in a mouse model of aging-induced OA. Methods: Wild-type (WT) and Panx3−/− C57BL/6J (Black-6) mice, ages 18–24 months, were analyzed by micro–computed tomography to investigate bone mineral density and body composition. Joints were harvested from the mice, and histopathologic analysis of the joint tissue for OA development was conducted with a specific focus on changes in articular cartilage, subchondral bone, and synovial tissue. Results: Global loss of Panx3 in aging mice was not associated with increased mortality or changes in body composition. Mice lacking Panx3 had shorter appendicular skeletons than WT mice, but overall the body compositions appeared quite similar. Panx3 deletion dramatically accelerated cartilage degeneration and subchondral bone thickening with aging in both 18-month-old and 24-month-old mice, while promoting synovitis in 18-month-old mice. Conclusion: These observations in a mouse model of OA suggest that Panx3 has a protective role against the development of primary aging-associated OA. It appears that Panx3 has opposing context-specific roles in joint health following traumatic injury versus that associated with aging. These data strongly suggest that there are differences in the molecular pathways driving different subtypes of OA, and therefore a detailed understanding of these pathways could directly improve strategies for OA diagnosis, therapy, and research.
