Increased intercellular communication through gap junctions may contribute to progression of osteoarthritis.
Our aim was to support the hypothesis of a specific association between gap junctions in synovial tissue and the presence of osteoarthritis, as evidenced by differences between osteoarthritis and non-osteoarthritis synovia in the number of gap junctions, the amount of gap-junction protein, and the amount of enzymatic activity produced through a pathway mediated by gap-junction intercellular communication. An average of 4.41 gap junctions were found per 100 cells counted in the osteoarthritis synovia, compared with 1.00 in the controls. The amount of the gap-junction protein connexin 43 in synovial lining cells was approximately 50% greater in patients with osteoarthritis. Synovial lining cells from patients with osteoarthritis produced matrix metalloproteinases constitutively and, at higher levels, in response to stimulation by interleukin-1 beta. In both cases, intercellular communication through gap junctions was shown to be critical to the ability of the cells to secrete matrix metalloproteinases. Overall, the results indicated that gap junctions between synovial lining cells were altered significantly in patients with osteoarthritis, as a consequence of the disease process or as part of the causal chain. In either case, gap junctions seem to be a rational therapeutic target.
Marino
Andrew A
AA
Department of Orthopaedic Surgery, LSU Health Sciences Center, Shreveport, LA 71130-3932, USA. amarino@lsuhsc.edu
Waddell
David D
DD
Kolomytkin
Oleg V
OV
Meek
William D
WD
Wolf
Robert
R
Sadasivan
Kalia K
KK
Albright
James A
JA
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D015153:Blotting, Western; D016022:Case-Control Studies; D002450:Cell Communication / Q000502:physiology*; D017630:Connexins / Q000032:analysis / Q000378:metabolism*; D046508:Culture Techniques; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000166:cytology / Q000473:pathology; D015854:Up-Regulation
D015415:Biomarkers; D017630:Connexins