title: Hyaluronan inhibits BMP-induced osteoblast differentiation.
abstract: Hyaluronan (HA), one of the major structural extracellular components in cartilage, regulates cellular responses via receptors such as CD44. However, the direct effects of HA on osteoblastic differentiation has not been studied in detail. Here, we investigated the effects of HA (molecular weight: 900-1200 kDa) on osteoblastic differentiation that was induced by bone morphogenetic protein (BMP) in C2C12 cells (mouse myoblastic cells) and ST2 cells (mouse bone marrow cells). BMP-induced osteoblastic differentiation and Smad1/Smad5/Smad8 phosphorylation were downregulated by HA. Use of the CD44-blocking antibody restored HA-induced inhibition of osteoblastic differentiation and Smad1/Smad5/Smad8 phosphorylation. Our results indicate that HA inhibits BMP-induced osteoblastic differentiation through the CD44 receptor.
authors.affiliation: Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Chikahisa
authors.initials: C
authors.lastname: Higuchi
authors.affiliation: Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kunugiza
authors.affiliation: Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.affiliation: Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan; Medicine for Sports and Performing Arts, Department of Health and Sport Sciences, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. Electronic address: ken-nakata@umin.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Nakata
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D051379:Mice; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000502:physiology*; D015183:Restriction Mapping; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D000469:Alkaline Phosphatase; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
keywords: Bone morphogenetic protein; CD44; Hyaluronan; Osteoblast