Hyaluronan and CD44: Strategic players for cell–matrix interactions during chondrogenesis and matrix assembly

Abstract

Embryonic induction, soluble and insoluble factors, receptors, and signal transduction are orchestrated for the morphogenesis of the cartilage elements. The interaction of cells with the extracellular matrix (ECM) may lead to altered cellular response to morphogens based on the formation of new adhesive contacts, or the uncoupling of cell-matrix interactions. Hyaluronan's influence on cell behavior, and its intimate association with cells are accomplished by a wide variety of specific binding proteins for hyaluronan. The temporal expression of the hyaluronan receptor CD44 (which is expressed as several alternatively spliced variants) may be strategic to many of these cell-matrix interactions during chondrogenesis. CD44 expression is temporally coincident with the reduction of intercellular spaces at the regions of future cartilage deposition. The spatial organization of CD44 at the cell surface may function to establish or regulate the structure of the pericellular matrix dependent on a hyaluronan scaffold. As the ECM is modified during embryogenesis, the cellular response to inductive signals may be altered. An uncoupling of chondrocyte-hyaluronan interaction leads to chondrocytic chondrolysis. Thus, consideration of cell-matrix interactions during chondrogenesis, in the light of our current understanding of the temporal and spatial expression of signaling morphogens, should become a promising focus of future research endeavors.

CD44 Variant Isoforms Promote Metastasis Formation by a Tumor Cell-Matrix Cross-talk That Supports Adhesion and Apoptosis Resistance

“…One could also speculate that endogenous hyaluronidase activity differs in dependence on CD44v expression or that hyaluronidase inhibitors or other matrix components protect the deposited hyaluronan (51,52). The requirement of CD44 for pericellular matrix assembly in chondrocytes has been suggested to proceed through hyaluronan anchoring (53,54). Yet, as outlined in these overviews, a better understanding of the hyaluronan metabolism is required to further elucidate the function of CD44v in tumor matrix assembly (53,54).…”

“…The requirement of CD44 for pericellular matrix assembly in chondrocytes has been suggested to proceed through hyaluronan anchoring (53,54). Yet, as outlined in these overviews, a better understanding of the hyaluronan metabolism is required to further elucidate the function of CD44v in tumor matrix assembly (53,54).…”

Three vertebrate hyaluronan synthases are expressed during mouse development in distinct spatial and temporal patterns

“…Initially, HA is associated with the migration of sclerotomal, mesodermal, and neural crest cells that give rise to the axial skeleton, the limb skeleton, and the branchial arches, craniofacial bones, and cartilage (Solursh et al, 1979;Knudson and Toole, 1985;Perris et al, 1991). During limb bud outgrowth, a large amount of extracellular HA may facilitate cell division (Knudson, 2003). HA levels rapidly decrease at the time of condensation when cells aggregate before the formation of individual cartilage or bone elements.…”

Addition of hyaluronic acid improves cellular infiltration and promotes early-stage chondrogenesis in a collagen-based scaffold for cartilage tissue engineering

“…The high anionic charge of HyA may alter the visco-elastic properties of the pericellular matrix surrounding cells and as a result, preventing cells from adhering firmly onto scaffolds struts possibly leading to increased migration (Toole, 2001, Chen andAbatangelo, 1999). Another mechanism by which cell migration could be occurring may be a result of intracellular signalling pathways initiated by the specific interaction of MSCs and HyA through cell receptors such as integrins, CD44 and RHAMM (Receptor for Hyaluronic Acid Mediated Motility) (Toole, 2001, Chen and Abatangelo, 1999, Friedl and Bröcker, 2000, Knudson, 2003. Indeed it has been shown that inhibition of CD44 receptor resulted in MSCs with a reduced motility on HyA coated surfaces (Zhu et al 2006).…”