Hyaluronan enhances cartilage repair through low grade tissue remodeling involving cytokines and matrix metalloproteinases

Abstract

These results collectively suggest that some of the repair activity of HA800 is through proteolytic activity which is not sufficient to decrease matrix PG content, but is nonetheless elevated above levels in cartilage not treated with HA800.

Silk fibroin/hyaluronan scaffolds for human mesenchymal stem cell culture in tissue engineering

“…While several reports indicate that HA induces expression of this structural protein [27,48,49], others observed downregulation when cells were cultured on HA scaffolds [25]. The general tendency is that scaffolds based on HA favor proliferation [50], inhibit the production of proteins that mediate cell attachment [25], up-regulate the expression of cartilage related genes [27,30,48,49,51], and modulate the expression of inflammatory and catabolic markers [49,51,52]. The relation between HA composition, bone related genes and extracellular matrix components (e.g.…”

Mechanisms of Beneficial Effects of High Molecular Weight Hyaluronan on Cultured Cartilage Tissue

“…Paradoxically, it was found that the various HA forms did enhance MMP-3 expression, cartilage matrix degradation neoepitopes and depletion of PG from cultured cartilage explants in serum free conditions. As the mass of HA increased up to the mass of 800-kDa, the ability of HA to enhance PG synthesis or to block Fn-f mediated damage or to repair cartilage increased but the ability to enhance proteolytic activity decreased [57]. However, with the larger mass HA forms from 20 to 800-kDa, the degradation was not sufficient to decrease steady state levels of PG.…”

“…It has been shown that higher mass HA forms do elevate MMP-3 and enhance PG degradation by 7 days in culture [57]. There is an inverse dose dependence between mass and matrix damage activity.…”

“…It has been proposed that culturing of cartilage with HA might induce sufficient matrix degradation to liberate IGF-I from inactive complexes with IGF binding proteins in the matrix or may liberate IGF-I through general matrix damage [57]. This proposal was based on observations that elevated protease activities can liberate IGF-I from the various cell matrices and activate IGF-I [58][59][60][61].…”

Bioactive Scaffolds for the Controlled Formation of Complex Skeletal Tissues

“…These interactions trigger signaling cascades that could result in the observed capacity of hyaluronan to instruct tissue neoformation and regeneration. For illustration, hyaluronan has shown pro-proliferative properties (Zou et al, 2004), capacity to enhance unspecific ECM deposition (Garcia-Fuentes et al, 2009), to induce cartilage (Allemann et al, 2001;Williams et al, 2003;Yamane et al, 2005) and ligament (Cristino et al, 2005) formation, capacity to maintain embryonic stem cells in undifferentiated state (Gerecht et al, 2007), and capacity to modulate inflammatory and catabolic markers Homandberg et al, 2004). Hyaluronan biological properties, though, seem to be very dependent on its molecular weight, and the presence of hyaluronan oligosaccharides have been connected to chondrocyte-driven chondrolysis (Knudson et al, 2000).…”