title: A Dual Role of Upper Zone of Growth Plate and Cartilage Matrix-Associated Protein in Human and Mouse Osteoarthritic Cartilage: Inhibition of Aggrecanases and Promotion of Bone Turnover.
abstract: Cartilage damage and subchondral bone changes are closely connected in osteoarthritis. Nevertheless, how these processes are interlinked is, to date, incompletely understood. This study was undertaken to investigate the mechanistic role of a cartilage-derived protein, upper zone of growth plate and cartilage matrix-associated protein (UCMA), in osteoarthritis-related cartilage and bone changes.
  
  
  
  UCMA expression was assessed in healthy and osteoarthritic human and mouse cartilage. For analysis of cartilage and bone changes, osteoarthritis was induced by destabilization of the medial meniscus (DMM) in wild-type (WT) and Ucma-deficient mice. UCMA-collagen interactions, the effect of UCMA on aggrecanase activity, and the impact of recombinant UCMA on osteoclast differentiation were studied in vitro.
  
  
  
  UCMA was found to be overexpressed in human and mouse osteoarthritic cartilage. DMM-triggered cartilage changes, including increased structural damage, proteoglycan loss, and chondrocyte cell death, were aggravated in Ucma-deficient mice compared to WT littermates, thereby demonstrating the potential chondroprotective effects of UCMA. Moreover, UCMA inhibited ADAMTS-dependent aggrecanase activity and directly interacted with cartilage-specific collagen types. In contrast, osteoarthritis-related bone changes were significantly reduced in Ucma-deficient mice, showing less pronounced osteophyte formation and subchondral bone sclerosis. Mechanistically, UCMA directly promoted osteoclast differentiation in vitro.
  
  
  
  UCMA appears to link cartilage with bone changes in osteoarthritis by supporting cartilage integrity as an endogenous inhibitor of aggrecanases while also promoting osteoclastogenesis and subchondral bone turnover. Thus, UCMA represents an important link between cartilage and bone in osteoarthritis.
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stock
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Menges
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Eitzinger
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Geßlein
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Renate
authors.initials: R
authors.lastname: Botschner
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Wormser
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Alfiya
authors.initials: A
authors.lastname: Distler
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Schlötzer-Schrehardt
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Dietel
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Distler
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Beyer
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Kolja
authors.initials: K
authors.lastname: Gelse
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Engelke
authors.affiliation: Radboud University, Nijmegen, The Netherlands.
authors.forename: Marije I
authors.initials: MI
authors.lastname: Koenders
authors.affiliation: Radboud University, Nijmegen, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: van den Berg
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: von der Mark
authors.affiliation: Friedrich Alexander University of Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D002358:Cartilage, Articular / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D019902:Chondrocytes / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D006132:Growth Plate / Q000378:metabolism*; D006801:Humans; D064235:Matrilin Proteins / Q000378:metabolism*; D051379:Mice; D010003:Osteoarthritis / Q000473:pathology / Q000503:physiopathology*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology; D011509:Proteoglycans / Q000378:metabolism
chemical_list: D064235:Matrilin Proteins; D011509:Proteoglycans; D010450:Endopeptidases; C083641:aggrecanase