title: Accelerated development of aging-associated and instability-induced osteoarthritis in osteopontin-deficient mice.
abstract: OBJECTIVE
  To investigate the role of osteopontin (OPN) in the development of osteoarthritis (OA) under in vivo and in vitro conditions.
  
  
  METHODS
  Both instability-induced and aging-associated OA models were generated using OPN-deficient (OPN-/-) and control wild-type (WT) mice. An in vitro cartilage degradation model was also used, to evaluate the effect of OPN on proteoglycan loss from joint cartilage.
  
  
  RESULTS
  OPN deficiency exacerbated both aging-associated and instability-induced OA. Both structural changes and an increased loss of proteoglycan from cartilage tissue were augmented in the absence of OPN. OPN deficiency also led to the induction of matrix metalloproteinase 13 (MMP-13), which degrades a major component of the cartilage matrix protein type II collagen. Both the loss of proteoglycan and the induction of the collagen-degrading enzyme MMP-13 facilitated the development of OA.
  
  
  CONCLUSIONS
  OPN plays a pivotal role in the progression of both instability-induced and aging-associated spontaneous OA. OPN is a critical intrinsic regulator of cartilage degradation via its effects on MMP-13 expression and proteoglycan loss.
authors: Institute for Genetic Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Yuichiro
authors: Y
authors: Matsui
authors: Norimasa
authors: N
authors: Iwasaki
authors: Shigeyuki
authors: S
authors: Kon
authors: Daisuke
authors: D
authors: Takahashi
authors: Junko
authors: J
authors: Morimoto
authors: Yutaka
authors: Y
authors: Matsui
authors: David T
authors: DT
authors: Denhardt
authors: Susan
authors: S
authors: Rittling
authors: Akio
authors: A
authors: Minami
authors: Toshimitsu
authors: T
authors: Uede
mesh_terms: D000375:Aging; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007593:Joint Instability / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D053495:Osteopontin / Q000172:deficiency* / Q000235:genetics; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013264:Stifle / Q000378:metabolism / Q000473:pathology / Q000601:surgery
chemical_list: D011509:Proteoglycans; D012333:RNA, Messenger; D053495:Osteopontin; D053509:Matrix Metalloproteinase 13