title: Elimination of BMP7 from the developing limb mesenchyme leads to articular cartilage degeneration and synovial inflammation with increased age.
abstract: While osteo- and chondro-inductive activities of recombinant human bone morphogenetic protein 7 are well established, evaluation of the role of endogenous BMP7 in skeletal homeostasis has been hampered by perinatal lethality in BMP7 knockout mice. Here, we examined physiological roles of endogenous BMP7 in joint homeostasis and showed that proteoglycan contents in articular cartilage were significantly reduced in the absence of BMP7. Loss of BMP7 did not affect survival of articular cartilage cells, but resulted in reduced expression of aggrecan and enhanced expression of matrix metalloproteinase 13. We also found extensive synovial hyperplasia and enhanced expression of Activin A. These findings suggest that locally produced BMP7 is prerequisite for postnatal synovial joint homeostasis and may be involved in osteoarthritic changes in adults.
authors.affiliation: Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Japan.
authors.forename: Kahaer
authors.initials: K
authors.lastname: Abula
authors.affiliation: Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Muneta
authors.affiliation: Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Miyatake
authors.affiliation: Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Yamada
authors.affiliation: Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Matsukura
authors.affiliation: Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sekiya
authors.affiliation: School of Dentistry, University of Alberta, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Graf
authors.affiliation: Regeneron Pharmaceuticals Inc., United States.
authors.forename: Aris N
authors.initials: AN
authors.lastname: Economides
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, United States.
authors.forename: Vicki
authors.initials: V
authors.lastname: Rosen
authors.affiliation: Department of Cartilage Regeneration, Graduate School, Tokyo Medical and Dental University, Japan. Electronic address: tsuji.orj@tmd.ac.jp.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tsuji
mesh_terms: D028341:Activins / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D053674:Aggrecans / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000096:biosynthesis* / Q000235:genetics; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006614:Hindlimb / Q000196:embryology / Q000473:pathology; D006801:Humans; D008648:Mesoderm / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013585:Synovitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D053674:Aggrecans; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; C422405:activin A; C525820:bmp7 protein, mouse; D028341:Activins
keywords: Activin A; Articular cartilage; Bone morphogenetic protein 7; Osteoarthritis; Proteoglycan; Synovitis