Protection from interleukin 1 induced destruction of articular cartilage by transforming growth factor beta: studies in anatomically intact cartilage in vitro and in vivo.

Abstract

The modulation of interleukin 1 (IL-1) effects on proteoglycan metabolism in intact murine patellar cartilage by transforming growth factor P (TGF-I) was investigated in vitro and in vivo. In vitro TGF-,1 (400 pmol/) had no effect on basal proteoglycan degradation. Proteoglycan degradation induced by IL-1, however, was suppressed by TGF-j in serum free medium alone and in medium supplemented with 0.5 ,ug/mi insulin-like growth factor 1. This suggests a specific regulatory role for TGF-I under pathological conditions. In contrast with the suppression of breakdown, synthesis of proteoglycans was stimulated by TGF-iS for both basal and IL-1 suppressed proteoglycan synthesis in cultures without insulin-like growth factor. In the presence of insulin-like growth factor no extra effect of TGF-(8 on proteoglycan synthesis was observed. With insulin-like growth factor, however, TGF-P potentiated the ex vivo recovery of IL-1 induced suppression of proteoglycan synthesis. Analogous to the in vitro effects, TGF-I8 injected intraarticularly suppressed IL-1 induced proteoglycan degradation. Furthermore, TGF-, injected into the joint counteracted IL-1 induced suppression of proteoglycan synthesis. This indicates that in vivo also TGF-, can ameliorate the deleterious effects of IL-1 on the cartilage matrix.

Inhibition of Endogenous TGF-β During Experimental Osteoarthritis Prevents Osteophyte Formation and Impairs Cartilage Repair

“…injection of TGF-␤ during experimental arthritis resulted in protection from PTG loss (15). In addition, effects of IL-1, such as inhibition of cartilage PTG synthesis and release of cartilage PTG content, could be blocked by local application of TGF-␤ (16,17). This demonstrates that TGF-␤ is able to counteract the deleterious effects of IL-1, a cytokine considered to be a key mediator during erosive joint diseases.…”

Stimulation of TIMP‐1 production by oncostatin m in human articular cartilage

“…However, our results exhibited an additive, rather than synergistic, effect. Another important action of TGFP is the suppression of MMPs stimulated by IL-1 in vitro and in vivo (41,42). OSM did not alter the basal levels of MMP-1 and MMP-3 in this study, and we are currently attempting to investigate whether OSM could modulate JL-1-induced MMP production.…”

Differential regulation of lubricin/superficial zone protein by transforming growth factor β/bone morphogenetic protein superfamily members in articular chondrocytes and synoviocytes

“…The TGF␤ family consists of 3 isoforms, TGF␤1, TGF␤2, and TGF␤3, in humans and mice. TGF␤ is an important anabolic factor in articular cartilage (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). BMPs are related to TGF␤ and have fundamental roles in the initiation and maintenance of articular cartilage (41)(42)(43).…”