IL-1ß and BMPs - Interactive players of cartilage matrix degradation and regeneration

Abstract

Intact human adult articular cartilage is central for the functioning of the articulating joints. This largely depends on the integrity of its extracellular matrix, given the high loading forces during movements in particular in the weight-bearing joints. Unlike the first impression of a more or less static tissue, articular cartilage shows -albeit in the adult organism -a slow tissue turnover. Thus, one of the most important questions in osteoarthritis research is to understand the balance of catabolic and anabolic factors in articular cartilage as this is the key to understand the biology of cartilage maintenance and degeneration.Anabolic and catabolic pathways are very much intermingled in articular cartilage. The balance between anabolism and catabolism is titrated on numerous levels, starting from the mediator-synthesizing cells which express either catabolic or anabolic factors. Also, on the level of the effector cells (i.e. chondrocytes) anabolic and catabolic gene expression compete for a balance of matrix homeostasis, namely the synthesis of matrix components and the expression and activation of matrix-degrading proteases. Also, there are multiple layers of intracellular cross-talks in between the anabolic and catabolic signalling pathways. Maybe the most important lesson from this overview is the notion that the anabolic-catabolic balance as such counts and not so much sufficient net anabolism or limited catabolism alone. Thus, it might be neither the aim of osteoarthritis therapy to foster anabolism nor to knock down catabolism, but the balance of anabolic-catabolic activities as a total needs proper titration and balancing.

Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis

“…In osteoarthritis, catabolism becomes stronger than the anabolic capacities of chondrocytes, the cartilage matrix degenerates, and the joint cartilage gets damaged. 34 We speculate that MSCs were mobilized from SYN through SF toward degenerative cartilage. Seemingly, the number of mobilized MSCs is limited, therefore osteoarthritis progresses in its natural course.…”

Activation of Interleukin-1 Signaling Cascades in Normal and Osteoarthritic Articular Cartilage

“…These results suggest the presence of a complex interwoven network of cytokines and growth factors responsible for tissue homeostasis and pathology. 33,40 The importance of IL-1 in joint and cartilage homeostasis is clearly documented by the arthritic and degenerative changes that occur in knockout mice of IL-1 and its processing molecules 34,41 in addition to the genetic association of the IL-1/IL-1 receptor gene cluster with osteoarthritis development. 42 …”

Resistance exercise recovers the structure of cartilage and synovial membrane of the ankle joint of rats after sciatic compression

“…Since the nerve lesions interrupt neuromuscular communication, which can lead to atrophy of the effector muscles 8,31,32 , the biomechanics of the ankle are compromised, causing a reduction in the range of motion of the joint 33 and a decrease in weight loss in the affected limb. As a consequence, changes in joint structures, such as those cited in the present study, occur because of the influence that load transfer plays on the joint tissues homeostasis 34,35 . In both tibia and talus, the thickness of the articular cartilage was not changed by the sciatic nerve lesion (LG), stair climbing exercise (EG) or exercise after lesion (LEG).…”