title: Up-regulation of proteoglycan 4 in temporomandibular osteoarthritic synovial cells by hyaluronic acid.
abstract: BACKGROUND
  Hyaluronic acid (HA) injection is widely used in the treatment of temporomandibular joint (TMJ) osteoarthritis (OA). Proteoglycan 4 (PRG4) is another joint lubricant that protects surface of articular cartilage. But few studies had explored the role of HA in regulation of PRG4 expression in TMJ OA. In this study, the effects of HA on the expression of PRG4 in osteoarthritic TMJ synovial cells were investigated in hypoxia, which was similar to the TMJ physiologically.
  
  
  METHODS
  Synovial cells were isolated from the TMJ OA patients and were treated with or without HA under normoxia or hypoxia for indicated time periods. The proliferation of synovial cells was measured using Cell Counting Kit-8 (CCK-8). The gene expression of HAS2, VEGF, and PRG4 was detected by quantitative real-time PCR, and the secretion of PRG4 and VEGF was assayed by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to examine the protein expression of hypoxia-induced factor-1α (HIF-1α).
  
  
  RESULTS
  Hyaluronic acid markedly increased the proliferation of osteoarthritic synovial cells in hypoxia. The expression of HAS2 and PRG4 mRNA of osteoarthritic synovial cells under hypoxia was enhanced by HA treatment. However, HA had no effect on reducing the VEGF and HIF-1α expression in synovial cells in hypoxia.
  
  
  CONCLUSIONS
  Hyaluronic acid could promote the expression of HAS2 and PRG4, but could not modulate HIF-1α and VEGF expression of TMJ osteoarthritic synovial cells in hypoxia.
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Guo
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.|Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ke
authors.affiliation: Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Mohong
authors.initials: M
authors.lastname: Deng
authors.affiliation: Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Qinggong
authors.initials: Q
authors.lastname: Meng
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Long
mesh_terms: D000328:Adult; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D003239:Connective Tissue Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013704:Temporomandibular Joint / Q000378:metabolism / Q000473:pathology; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D000099158:Proteoglycan 4
chemical_list: D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C497442:HIF1A protein, human; C419197:PRG4 protein, human; D000099158:Proteoglycan 4; C467484:VEGFA protein, human; C101754:HAS2 protein, human
keywords: hyaluronan synthase 2; hyaluronic acid; osteoarthritis; proteoglycan 4; temporomandibular joint