title: The role of subchondral bone resorption pits in osteoarthritis: MMP production by cells derived from bone marrow.
abstract: OBJECTIVE
  The vascular invasion of bone marrow tissue into the subchondral plate is often observed in articular cartilage and we named it the subchondral bone absorption pit; however, its implication in the pathogenesis of osteoarthritis (OA) has been poorly understood. The purpose of this study was to evaluate its characteristics and roles in osteoarthritic conditions.
  
  
  METHODS
  Articular cartilage specimens from 11 patients with medial type knee OA and 7 non-arthritic cadavers were analyzed with HE staining. OA sections were stained with safranin-O, TRAP (tartrate resistant acid phosphatase) and immunostained with anti-MMP-1, MMP-3, MMP-13, vitronectin receptor (VNR)-alpha chain, vimentin and bone morphogenic protein (BMP) 2/4 antibodies.
  
  
  RESULTS
  Subchondral bone resorption pits were classified according to the extent of invasion: pits with bone marrow tissue were located within uncalcified cartilage below the tidemark in grade I and invaded beyond the tidemark in grade II, while no invasion was seen in grade 0. Grade II pits were dominant in OA compared to non-arthritic joints, especially medial condyles. Proteoglycan detected with safranin-O staining was lost around the tip of grade II pits and the density of pits was related to the modified Mankin Score. Cells in pits expressed vimentin, MMP-1, MMP-3 and MMP-13. Some polynuclear cells co-expressed VNR-alpha chain and MMP-13, whereas pits showed reparative features expressing BMP.
  
  
  CONCLUSIONS
  These results suggest that subchondral bone resorption pits contribute to cartilage degradation by expressing matrix metalloproteinases in OA.
authors.affiliation: Department of Bioregulation and Proteomics, Institute of Medical Science, St. Marianna University, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8512, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Shibakawa
authors.forename: K
authors.initials: K
authors.lastname: Yudoh
authors.forename: K
authors.initials: K
authors.lastname: Masuko-Hongo
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Nishioka
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells / Q000201:enzymology*; D019485:Bone Morphogenetic Proteins / Q000032:analysis; D016723:Bone Remodeling / Q000502:physiology; D001862:Bone Resorption / Q000378:metabolism / Q000503:physiopathology*; D002102:Cadaver; D002358:Cartilage, Articular / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D017364:Collagenases / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000032:analysis*; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000503:physiopathology*; D011509:Proteoglycans / Q000378:metabolism; D014746:Vimentin / Q000032:analysis; D019096:Vitronectin / Q000032:analysis
chemical_list: D019485:Bone Morphogenetic Proteins; D011509:Proteoglycans; D014746:Vimentin; D019096:Vitronectin; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1