title: Osteopontin Deficiency Suppresses Tumor Necrosis Factor-α-Induced Apoptosis in Chondrocytes.
abstract: OBJECTIVE
  Apoptosis of chondrocytes in articular cartilage has been observed in rheumatoid arthritis patients. However, molecules involved in such chondrocyte apoptosis in arthritic joints have not been fully understood. We previously observed that apoptosis of chondrocytes is enhanced in a murine arthritis model induced by injection with anti-type II collagen antibodies and lipopolysaccharide (mAbs/LPS), and osteopontin (OPN) deficiency suppresses chondrocyte apoptosis in this arthritis model in vivo. To understand how OPN deficiency renders resistance against chondrocyte apoptosis, we examined the cellular basis for this protection.
  
  
  METHODS
  Chondrocytes were prepared from wild-type and OPN-deficient mouse ribs, and tumor necrosis factor (TNF)-α-induced cell death was examined based on lactate dehydrogenase (LDH) release assay and TUNEL assay.
  
  
  RESULTS
  TNF-α treatment induced LDH release in wild-type chondrocytes, while OPN deficiency suppressed such LDH release in the cultures of these cells. TNF-α-induced increase in the number of TUNEL-positive cells was observed in wild-type chondrocytes, while OPN deficiency in chondrocytes suppressed the TNF-α induction of TUNEL-positive cells. OPN deficiency suppressed TNF-α-induced increase in caspase-3 activity in chondrocytes in culture. Furthermore, OPN overexpression in chondrocytes enhanced TNF-α-induced apoptosis.
  
  
  CONCLUSIONS
  These results indicated that the presence of OPN in chondrocytes is involved in the susceptibility of these cells to TNF-α-induced apoptosis.
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yumoto
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nifuji
authors.affiliation: Rutgers University, Piscataway, NJ, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Rittling
authors.affiliation: Immuno Biological Laboratory (IBL), Maebashi Gumma, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuchiya
authors.affiliation: Hokkaido University, Sapporo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kon
authors.affiliation: Hokkaido University, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Uede
authors.affiliation: Rutgers University, Piscataway, NJ, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Denhardt
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan ; Medical Top Track (MTT) Program, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hemmi
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Notomi
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan ; Global Center of Excellence Program, Tokyo Medical and Dental University, Tokyo, Japan ; Core to Core Program, Tokyo Medical and Dental University, Tokyo, Japan ; Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hayata
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan ; Global Center of Excellence Program, Tokyo Medical and Dental University, Tokyo, Japan ; Core to Core Program, Tokyo Medical and Dental University, Tokyo, Japan ; Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ezura
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan ; Global Center of Excellence Program, Tokyo Medical and Dental University, Tokyo, Japan ; Core to Core Program, Tokyo Medical and Dental University, Tokyo, Japan ; Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakamoto
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan ; Medical Top Track (MTT) Program, Tokyo Medical and Dental University, Tokyo, Japan ; Global Center of Excellence Program, Tokyo Medical and Dental University, Tokyo, Japan ; Core to Core Program, Tokyo Medical and Dental University, Tokyo, Japan ; Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Noda
keywords: animal models < general; biomechanics < general; chondrocytes < cells; chondrogenesis < cells