TY - JOUR
T1 - Increased intercellular communication through gap junctions may contribute to progress of osteoarthritis
AU - Marino, Andrew A.
AU - Waddell, David D.
AU - Kolomytkitn, Oleg V.
AU - Meek, William D.
AU - Wolf, Robert
AU - Sadasivan, Kalia K.
AU - Albright, James A.
PY - 2004/1/1
Y1 - 2004/1/1
N2 - 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-1β. 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.
AB - 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-1β. 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.
UR - http://www.scopus.com/inward/record.url?scp=2542463079&partnerID=8YFLogxK
U2 - 10.1097/01.blo.0000129346.29945.3b
DO - 10.1097/01.blo.0000129346.29945.3b
M3 - Article
C2 - 15187861
AN - SCOPUS:2542463079
SN - 0009-921X
VL - 422
SP - 224
EP - 232
JO - Clinical Orthopaedics and Related Research
JF - Clinical Orthopaedics and Related Research
IS - 422
ER -