Gap Junctions in Osteoarthritis

David D. Waddell1, Andrew A. Marino2, Oleg V. Kolomytkin2, William D. Meek3, Robert E. Wolf2, Kalia K. Sadasivan2, and James A. Albright2. (1) Orthopaedic Research Specialists, Shreveport, LA, USA. (2) LSU Health Sciences Center, Shreveport, LA, USA. (3) University of Oklahoma, Tulsa, OK, USA.

Presented at American Academy of Orthopaedic Surgeons 2002 Annual Meeting; Dallas, Texas, February 2002.


Abstract

Synovial cells are electrically and metabolically coupled through gap junctions (GJs) composed of connexin43 protein, but their specific role in synovial tissue is unknown. We hypothesized that synovial GJs were correlated with the presence of joint disease. Tissue biopsies were obtained from the fat pad of 11 patients with grade-four osteoarthritis (OA), and from 10 non-arthritic patients, and analyzed by SDS-PAGE for connexin43 using Western blots and by electron microscopy (EM).

Connexin43 was 50% greater in the OA patients (relative intensities of Western blots, 12.4 ± 2.0 compared with 8.2 ± 0.08, P < 0.05). In the EM study, regular 2-nm intermembrane gap separations characteristic of GJs were found in all tissues. The structures were about 1 μm in length, and usually occurred in cell processes. GJ hemichannels could frequently be resolved on the basis of periodic density changes. A minimum of 500 cells from each patient were examined, and the number of GJs in the OA patients was more than 4 times that of the controls (4.41 ± 2.21 compared with 1.00 ± 0.71 GJ/100 cells, P < 0.05). Considering that he arthritic synovial layer was generally thicker than normal, it can be concluded that the absolute number of gap junctions in the arthritic knees was far greater than normal. Whether GJs are a cause or a consequence of the disease remains to be determined. In either case, however, it is reasonable to suppose that GJs could serve as therapeutic targets to interrupt disease progression.

In summary, gap junctions were more prevalent in patients with osteoarthritis, suggesting that gap junctions might be effective therapeutic targets.

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