Transforming growth factor-beta stimulates retinoic acid-induced proteoglycan depletion in intact articular cartilage.
Cartilage-bearing sesamoid bones from the metacarpophalangeal joints of adult cows were cultured with retinoic acid for 1 week and allowed to recover in control medium for another 2 weeks. Retinoic acid decreased the proteoglycan synthesis of the cartilage to 33% of control values, and induced 26% loss of proteoglycans from the matrix. During recovery, the synthesis of proteoglycans returned to the control level but their content remained reduced. Transforming growth factor-beta (TGF-beta 1, 5 ng/ml) was added to the culture medium to stimulate the recovery. However, TGF-beta depressed the synthesis of proteoglycans and increased their loss to 61%. Only the large aggregating species, aggrecan, was lost from the matrix. The half-life of proteoglycans synthesized during recovery in control medium was 12.7 days, which was reduced to 8.7 days by TGF-beta. The proteoglycan half-life in control cartilage cultured without retinoic acid or TGF-beta was 33.8 days. Neither retinoic acid nor TGF-beta-induced changes in the hyaluronate content of the tissue. Aggrecans and small proteoglycans synthesized in the presence of TGF-beta were larger than those in controls. The synthesis of the small proteoglycans was stimulated 4.5-fold by TGF-beta, and their content was increased. The results show that TGF-beta can stimulate depletion of aggrecan in retinoic acid-treated cartilage. This indicates a catabolic function of TGF-beta in cartilage remodeling.
Von den Hoff
H W
HW
Jan van Breemen Instituut, Center for Rheumatology and Rehabilitation, Amsterdam, The Netherlands.
de Koning
M H
MH
van Kampen
G P
GP
van der Korst
J K
JK
D053674:Aggrecans; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016326:Extracellular Matrix Proteins; D005260:Female; D037181:Lectins, C-Type; D009924:Organ Culture Techniques; D011509:Proteoglycans / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D014212:Tretinoin