The role of the cartilage matrix in osteoarthritis

Abstract

Osteoarthritis (OA) involves all the structures of the joint. How the disease is initiated and what factors trigger the disease process remain unclear, although the mechanical environment seems to have a role. Our understanding of the biology of the disease has been hampered by the lack of access to tissue samples from patients with early stage disease, because clinically recognizable symptoms appear late in the osteoarthritic process. However, new data about the early processes in articular cartilage and new tools to identify the early stages of OA are providing fresh insights into the pathological sequence of events. The progressive destruction of cartilage involves degradation of matrix constituents, and rather active, yet inefficient, repair attempts. The release of fragmented molecules provides opportunities to monitor the disease process in patients, and to investigate whether these fragments are involved in propagating OA, for example, by inducing inflammation. The role of bone has not been fully elucidated, but changes in bone seem to be secondary to alterations in articular cartilage, which change the mechanical environment of the bone cells and induce them, in turn, to modulate tissue structure.

Matrix cross-linking–mediated mechanotransduction promotes posttraumatic osteoarthritis

“…The dense aggregates of negatively charged proteoglycans provide resistance to compressive loading by promoting osmotic swelling, which is counterbalanced by cross-linked collagen fibrils that confer tissue tensile strength. Disruption of this delicate balance leads to structural damage and functional failure of articular cartilage and, consequently, to development of osteoarthritis (OA), the most common arthropathy (4,5). OA cartilage ECM undergoes extensive remodeling, characterized by a decrease in matrix compliance (6,7).…”

Osteoarthritis, a disease bridging development and regeneration

“…The specific properties of these extracellular matrix molecules provide the articular cartilage its biomechanical characteristics. 10 The collagen fibers are responsible for resistance against tensile stretch, whereas the abundant negative charges on the macro-molecular proteoglycans attract water molecules that can be shifted within the tissue, giving its capacity to deform and adapt upon loading. The articular chondrocytes synthesize their own matrix and have distinct characteristics according to the layer of the cartilage where they reside.…”

“…However, once the fibrous network is also degraded, irreversible cartilage damage is likely. 10 Proof of principle studies in rodent models have shown that ADAMTS and MMPs can be successfully targeted. Nevertheless, the translation of these concepts into successful human clinical trials and market approval for drugs has been proven difficult as the effect size was not large or unexpected systemic toxicity excluded further development of the drugs.…”

“…1,5,10 Some of the cells, in particular in the deeper layers of the cartilage, start expressing markers of chondrocyte hypertrophy including expression of collagen type X. The concurrent change in matrix composition and increased calcification is likely changing the biomechanical properties of the tissue and further contributing to its progressive destruction.…”

Update on biological therapies for knee injuries: osteoarthritis

“…During cartilage degradation, fragments of matrix components are released, such as aggrecan, collagen, and fibromodulin fragments, which maintain inflammatory cytokine production [7]. Furthermore, oxide synthase 2, cyclooxygenase (COX)-2, and prostaglandin E gene expression are increased as well, contributing to articular inflammation and destruction by enhancing the activation and production of MMPs and the inhibition of type II collagen proteoglycan synthesis [10].…”