Cell-matrix adhesion is one of the important interactions that regulate stem cell survival, self-renewal, and differentiation. Our previous report indicated that a microenvironment enriched with hyaluronan (HA) initiated and enhanced chondrogenesis in human adipose derived stem cells (hADSCs). We further hypothesize that HA-induced chondrogenesis in hADSCs is mainly due to the interaction of HA and CD44 (HA-CD44), a cell surface receptor of HA. The HA-CD44 interaction was tested by examining the mRNA expression of hyaluronidase-1 (Hyal-1) and chondrogenic marker genes (SOX-9, collagen type II, and aggrecan) in hADSCs cultured on HA-coated wells. Cartilaginous matrix formation, sulfated glycosaminoglycan (sGAG) and collagen productions by hADSCs affected by HA-CD44 interaction were tested in a 3D fibrin hydrogel. About 99.9% of hADSCs possess CD44. The mRNA expressions of Hyal-1 and chondrogenic marker genes were up-regulated by HA in hADSCs on HA-coated wells. Blocking HA-CD44 interaction by anti-CD44 antibody completely inhibited Hyal-1 expression and reduced chondrogenic marker gene expression, which indicates that HA induced chondrogenesis in hADSCs mainly acts through HA-CD44 interaction. A two-hour pre-incubation and co-culture of cells with HA in hydrogel (HA/fibrin hydrogel) not only assisted in hADSC survival but also enhanced expression of Hyal-1 and chondrogenic marker genes. Higher levels of sGAG and total collagen were also found in HA/fibrin hydrogel group. Immunocytochemistry showed more collagen type II but less collagen type X in HA/fibrin than in fibrin hydrogels. Our results indicate that signaling triggered by HA-CD44 interaction significantly contributes to HA-induced chondrogenesis and may be applied to ADSC-based cartilage regeneration.

Hyaluronan (also called hyaluronic acid or hyaluronate or HA) is an anionic,nonsulfated glycosaminoglycan distributed widely throughout connective,epithelial, and neural tissues. It is unique among glycosaminoglycans in that it is nonsulfated, forms in the plasma membrane instead of the Golgi, and can be very large, with its molecular weight often reaching the millions.^[2] One of the chief components of the extracellular matrix, hyaluronan contributes significantly to cell proliferation and migration, and may also be involved in the progression of some malignant tumors.

The average 70 kg (154 lbs) person has roughly 15 grams of hyaluronan in the body, one-third of which is turned over (degraded and synthesized) every day.^[3]Hyaluronic acid is also a component of the group A streptococcal extracellularcapsule,^[4] and is believed to play a role in virulence.^[5][6]

1. Hyaluronate Sodium in the ChemIDplus database, consulté le 12 février 2009
2. Frasher, J.R.E et al’; Laurent, T. C.; Laurent, U. B. G. (1997).“Hyaluronan: its nature, distribution, functions and turnover”(PDF). Journal of Internal Medicine 242 (1): 27–33.doi:10.1046/j.1365-2796.1997.00170.x. PMID 9260563. Retrieved 2009-06-05.
3. Stern R (August 2004). “Hyaluronan catabolism: a new metabolic pathway”. Eur J Cell Biol 83 (7): 317–25.doi:10.1078/0171-9335-00392. PMID 15503855.
4. Sugahara, K.; N.B. Schwartz and A. Dorfman (1979).“Biosynthesis of hyaluronic acid by Streptococcus“. Journal of Biological Chemistry 254 (14): 6252–6261. PMID 376529.
5. Wessels, M.R.; A.E. Moses, J.B. Goldberg and T.J. DiCesare (1991). “Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci”. PNAS 88 (19): 8317–8321.doi:10.1073/pnas.88.19.8317. PMC 52499.PMID 1656437.
6.  Schrager, H.M.; J.G. Rheinwald and M.R. Wessels (1996).“Hyaluronic acid capsule and the role of streptococcal entry into keratinocytes in invasive skin infection”. Journal of Clinical Investigation 98 (9): 1954–1958. doi:10.1172/JCI118998.PMC 507637. PMID 8903312.

Hyaluronic Acid