TY - JOUR
T1 - Doxycycline disrupts chondrocyte differentiation and inhibits cartilage matrix degradation
AU - Cole, Ada A.
AU - Chubinskaya, Susan
AU - Luchene, Lawrence J.
AU - Chlebek, Kim
AU - Orth, Michael W.
AU - Greenwald, Robert A.
AU - Kuettner, Klaus E.
AU - Schmid, Thomas M.
PY - 1994/12
Y1 - 1994/12
N2 - Objective. The effects of doxycycline were tested in an in vitro system in which the cartilages of embryonic avian tibias are completely degraded. Methods. Tibias were cultured with 5, 20, or 40 μg/ml doxycycline. Control tibias were cultured without doxycycline. Conditioned media and tissue sections were examined for enzyme activity and matrix loss. Results. Cartilages were not resorbed in the presence of doxycycline, whereas control cartilages were completely degraded. Collagen degradation was reduced in association with treatment with doxycycline at all doses studied. Higher concentrations of doxycycline reduced collagenase and gelatinase activity and prevented proteoglycan loss, cell death, and deposition of type X collagen in the cartilage matrix; in addition, treatment with doxycycline at higher concentrations caused increases in the length of the hypertrophic region. Conclusion. The effects of doxycycline extend beyond inhibition of the proteolytic enzymes by stimulating cartilage growth and disrupting the terminal differentiation of chondrocytes.
AB - Objective. The effects of doxycycline were tested in an in vitro system in which the cartilages of embryonic avian tibias are completely degraded. Methods. Tibias were cultured with 5, 20, or 40 μg/ml doxycycline. Control tibias were cultured without doxycycline. Conditioned media and tissue sections were examined for enzyme activity and matrix loss. Results. Cartilages were not resorbed in the presence of doxycycline, whereas control cartilages were completely degraded. Collagen degradation was reduced in association with treatment with doxycycline at all doses studied. Higher concentrations of doxycycline reduced collagenase and gelatinase activity and prevented proteoglycan loss, cell death, and deposition of type X collagen in the cartilage matrix; in addition, treatment with doxycycline at higher concentrations caused increases in the length of the hypertrophic region. Conclusion. The effects of doxycycline extend beyond inhibition of the proteolytic enzymes by stimulating cartilage growth and disrupting the terminal differentiation of chondrocytes.
UR - http://www.scopus.com/inward/record.url?scp=0028050574&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028050574&partnerID=8YFLogxK
U2 - 10.1002/art.1780371204
DO - 10.1002/art.1780371204
M3 - Article
C2 - 7986218
AN - SCOPUS:0028050574
SN - 0004-3591
VL - 37
SP - 1727
EP - 1734
JO - Arthritis & Rheumatism
JF - Arthritis & Rheumatism
IS - 12
ER -