title: Hyaluronan initiates chondrogenesis mainly via CD44 in human adipose-derived stem cells.
abstract: Cell-matrix adhesion is one of the important interactions that regulates stem cell survival, self-renewal, and differentiation. Our previous report (Wu SC, Chang JK, Wang CK, Wang GJ, Ho ML. Biomaterials 31: 631-640, 2010) 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, and collagen productions by hADSCs affected by HA-CD44 interaction were tested in a three-dimensional fibrin hydrogel. About 99.9% of hADSCs possess CD44. The mRNA expressions of Hyal-1 and chondrogenic marker genes were upregulated 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 2-h preincubation and coculture 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 sulfated glycosaminoglycan 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 adipose-derived stem cell-based cartilage regeneration.
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Shun-Cheng
authors: SC
authors: Wu
authors: Chung-Hwan
authors: CH
authors: Chen
authors: Je-Ken
authors: JK
authors: Chang
authors: Yin-Chih
authors: YC
authors: Fu
authors: Chih-Kuang
authors: CK
authors: Wang
authors: Rajalakshmanan
authors: R
authors: Eswaramoorthy
authors: Yi-Shan
authors: YS
authors: Lin
authors: Yao-Hsien
authors: YH
authors: Wang
authors: Sung-Yen
authors: SY
authors: Lin
authors: Gwo-Jaw
authors: GJ
authors: Wang
authors: Mei-Ling
authors: ML
authors: Ho
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D020219:Chondrogenesis / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism* / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid
keywords: articular cartilage repair; human adipose-derived stem cells; hyaluronan-CD44 interaction; tissue engineering