Integrins and chondrocyte–matrix interactions in articular cartilage

Abstract

The integrin family of cell adhesion receptors plays a major role in mediating interactions between cells and the extracellular matrix. Normal adult articular chondrocytes express α1β1, α3β1, α5β1, α10β1, αVβ1, αVβ3, and αVβ5 integrins, while chondrocytes from osteoarthritic tissue also express α2β1, α4β1, α6β1. These integrins bind a host of cartilage extracellular matrix (ECM) proteins, most notably fibronectin and collagen types II and VI, which provide signals that regulate cell proliferation, survival, differentiation, and matrix remodeling. By initiating signals in response to mechanical forces, chondrocyte integrins also serve as mechanotransducers. When the cartilage matrix is damaged in osteoarthritis, fragments of fibronectin are generated that signal through the α5β1 integrin to activate a pro-inflammatory and pro-catabolic response which, if left unchecked, could contribute to progressive matrix degradation. The cell signaling pathways activated in response to excessive mechanical signals and to fibronectin fragments are being unraveled and may represent useful therapeutic targets for slowing or stopping progressive matrix destruction in arthritis.

The binding capacity of α1β1-, α2β1- and α10β1-integrins depends on non-collagenous surface macromolecules rather than the collagens in cartilage fibrils

“…3 for α2β1-integrin. In conclusion, these results confirm and extend previous observations [24,[39][40][41] that monomolecular cartilage collagens were good binding substrates for all collagen-binding integrins expressed by chondrocytes.…”

“…In agreement with this notion, we presented evidence here that the mostly non-collagenous components of collagen-containing fibrils in cartilage contain the relevant binding sites for integrins. Molecular candidates include collagen VI and microfibrils containing collagen VI [24], matrilins [11], COMP (thrombospondin 5) [13], and several SLRPs (decorin, fibromodulin, lumican) [44]. Many of these macromolecules have been associated also with a biomechanical role in cartilage (for review see [12]).…”

“…Here, we followed up on this subject by distinguishing the integrinmediated interactions of chondrocytes with cartilage collagens in molecular vs. fibrillar form. Integrinmediated cell-matrix-interactions influence cartilage homeodynamics and are disrupted during joint cartilage degeneration [21][22][23][24]. Chondrocyte surfaces contain distinct quantities of β1-integrins with α1-, α2-, and α10-chains, respectively.…”

Mesenchymal Stem Cells Inhibit Proteoglycan Degeneration in a Rat Model of Osteoarthritis

“…It was observed that some chondrocytes do not have the ability to migrate to damaged areas. Decrease in cell adhesion to fibronectin could be related to presence of apoptotic or necrotic chondrocytes in affected cartilage (22). Mesenchymal stem cells have the potential of differentiating into chondrocytes and can migrate to injured areas (23).…”

Modeling the formation of cell-matrix adhesions on a single 3D matrix fiber

“…These forces are transmitted to 20 the ECM through trans-membrane receptors of the integrin family placed on the cell membrane [9], which serve as traction points over which the cell moves as well as sources of migration-related regulatory signals [1,10,11,12]. These integrins are bound to the actin filaments in the cytoskeleton through a clutch of proteins that include talin, α-actinin, vinculin and paxilin [13,3,14].…”