title: Hypoxia-inducible factor-2α induces expression of type X collagen and matrix metalloproteinases 13 in osteoarthritic meniscal cells.
abstract: OBJECTIVE
  To evaluate whether Hypoxia-inducible factor-2α (HIF-2α) regulates expression of endochondral ossification-related molecules in human OA meniscus.
  
  
  METHODS
  Expressions of HIF-2α, type X collagen (COL10), matrix metalloproteinase (MMP)-13, and vascular endothelial growth factor (VEGF) in non-OA and OA menisci were analyzed by real-time RT-PCR and immunohistochemistry (IHC). Meniscal cells from OA patients were treated with interleukin-1β (IL-1β) and gene expression was analyzed. After knockdown of HIF-2α in OA meniscal cells, COL10 and MMP-13 expression were analyzed by RT-PCR, western blotting, immunofluorescence and ELISA.
  
  
  RESULTS
  Histological analysis demonstrated weak staining of the superficial layer and large round cells in OA meniscus. RT-PCR analysis showed that HIF-2α, COL10, MMP-13, and VEGF mRNA expressions were higher in OA than non-OA meniscal cells. IHC showed a coordinated staining pattern of HIF-2α, COL10, and MMP-13 in OA meniscus. IL-1β treatment increased HIF-2α, COL10, and MMP-13 expressions in OA meniscal cells, and knockdown of HIF-2α suppressed IL-1β-mediated increase in COL10 and MMP-13 expression.
  
  
  CONCLUSIONS
  These results suggested that HIF-2α may cause meniscal matrix degradation by transactivation of MMP-13. HIF-2α may be a therapeutic target for modulating matrix degradation in both articular cartilage and meniscus during knee OA progression.
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.|Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ishizuka
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. tadsakai@med.nagoya-u.ac.jp.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hiraiwa
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hamada
authors.affiliation: Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Warren
authors.initials: W
authors.lastname: Knudson
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.|Department of Orthopaedic Surgery, Tono Kosei Hospital, Mizunami, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Omachi
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Motoshige
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsukawa
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Oda
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takamatsu
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
mesh_terms: D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D000072600:Meniscus / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D024121:Collagen Type X; D053583:Interleukin-1beta; D053509:Matrix Metalloproteinase 13; D012333:RNA, Messenger; D000099162:Endothelial PAS Domain-Containing Protein 1; C507079:MMP13 protein, human
keywords: HIF-2α; Interleukin 1Β; Matrix metalloproteinase 13; Meniscal cell; Osteoarthritis; Type X collagen