title: Mineralization Effect of Hyaluronan on Dental Pulp Cells via CD44.
abstract: BACKGROUND
  CD44 is a cell-surface glycoprotein involved in various cellular functions. Recent studies have suggested that CD44 is involved in early mineralization of odontoblasts. Hyaluronic acid (HA) is the principal ligand for receptor CD44. Whether and how HA regulated the mineralization process of dental pulp cells were investigated.
  
  
  METHODS
  The effects of high-molecular-weight HA on differentiation and mineral deposition of dental pulp cells were tested by using alkaline phosphatase (ALP) activity assay and alizarin red S staining. Osteogenesis real-time polymerase chain reaction array, quantitative polymerase chain reaction, and Western blotting were performed to identify downstream molecules involved in the mineralization induction of HA. CD44 was knocked down and examined to confirm whether the mineralization effect of HA was mediated by receptor CD44. Immunohistochemistry was used to understand the localization patterns of CD44 and the identified downstream proteins in vivo.
  
  
  RESULTS
  Pulse treatment of HA enhanced ALP activity and mineral deposition in dental pulp cells. Tissue-nonspecific ALP, bone morphogenetic protein 7 (BMP7), and type XV collagen (Col15A1) were upregulated via the HA-CD44 pathway in vitro. Immunohistochemistry of tooth sections showed that the staining pattern of BMP7 was very similar to that of CD44.
  
  
  CONCLUSIONS
  Results of this study indicated that high-molecular-weight HA enhanced early mineralization of dental pulp cells mediated via CD44. The process involved important mineralization-associated molecules including tissue-nonspecific ALP, BMP7, and Col15A1. The findings may help develop new strategies in regenerative endodontics.
authors.affiliation: Department of Endodontics, ChiMei Medical Center, Tainan, Taiwan; Department of Dental Laboratory Technology, Min-Hwei College of Healthcare Management, Tainan, Taiwan.
authors.forename: Kuan-Liang
authors.initials: KL
authors.lastname: Chen
authors.affiliation: Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Yeh
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Jrhau
authors.initials: J
authors.lastname: Lung
authors.affiliation: Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Stomatology, National Cheng Kung University Hospital, Tainan, Taiwan. Electronic address: kuoyuan.tw@yahoo.com.tw.
authors.forename: Kuo
authors.initials: K
authors.lastname: Yuan
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000880:Anthraquinones; D015153:Blotting, Western; D055419:Bone Morphogenetic Protein 7 / Q000187:drug effects / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D058574:Integrin-Binding Sialoprotein / Q000187:drug effects / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000187:drug effects / Q000378:metabolism; D008964:Molar, Third / Q000166:cytology; D009804:Odontoblasts / Q000187:drug effects; D010012:Osteogenesis; D060888:Real-Time Polymerase Chain Reaction; D014074:Tooth Calcification / Q000187:drug effects*; D015854:Up-Regulation
chemical_list: D000880:Anthraquinones; D055419:Bone Morphogenetic Protein 7; C497483:CD44 protein, human; C085811:COL15A1 protein, human; D018960:Hyaluronan Receptors; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; C004468:Alizarin Red S; D006820:Hyaluronic Acid; D003094:Collagen; C548267:ALPL protein, human; D000469:Alkaline Phosphatase; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13
keywords: CD44; PCR array; dental pulp; hyaluronan; mineralization; odontoblast