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.