title: High molecular weight hyaluronic acid increases the differentiation potential of the murine chondrocytic ATDC5 cell line.
abstract: Osteoarthritis (OA) is a group of common, chronic, and painful inflammatory joint diseases. One important finding in OA patients is a remarkable decrease in the molecular weight of hyaluronic acid (HA) in the synovial fluid of affected joints. Therapeutic HA is available to patients in most parts of the world as a viscosupplementation product for the treatment of OA. Previous clinical reports show that high molecular weight HA (HMWHA) more effectively relieves pain than low molecular weight HA (LMWHA). However, the mechanism behind this finding remains unclear. In this study, we investigated whether a LMWHA (Low-0.9 MDa) and two types of HMWHA (High-1.9 MDa and 6 MDa) differentially affected chondroregulatory action. We tested this using ATDC5 cell, a murine chondrocytic cell line widely used in culture systems to study chondrogenic differentiation. We found that HMWHA, especially hylan G-F 20 (High-6 MDa), significantly induced aggrecan and proteoglycan accumulation, nodule formation, and mRNA expression of chondrogenic differentiation markers in a time- and dose-dependent manner. In addition, we showed that HMWHA prevented TNF-α induced inhibition of chondrogenic differentiation, with no effect on cell proliferation or viability. These results reveal that HMWHA significantly promotes chondrogenic differentiation of ATDC5 cells in vitro, and suggest that HMWHA plays a significant chondroregulatory role in vivo.
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan; Department of Orthopedic Surgery, Kikyougahara Hospital, Shiojiri, Nagano, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Sato
authors.forename: Takashi
authors.initials: T
authors.lastname: Ando
authors.forename: Jiro
authors.initials: J
authors.lastname: Ichikawa
authors.forename: Genki
authors.initials: G
authors.lastname: Okita
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Sato
authors.forename: Masanori
authors.initials: M
authors.lastname: Wako
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohba
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ochiai
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Hagino
authors.forename: Richard
authors.initials: R
authors.lastname: Jacobson
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Haro
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006820:Hyaluronic Acid / Q000494:pharmacology*; D051379:Mice; D008970:Molecular Weight; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D006820:Hyaluronic Acid
keywords: ATDC5; TNF-α; chondrogenesis; high molecular weight hyaluronic acid; osteoarthritis