The role of subchondral bone resorption pits in osteoarthritis: MMP production by cells derived from bone marrow

Osteoarthritis Cartilage. 2005 Aug;13(8):679-87. doi: 10.1016/j.joca.2005.04.010.

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.

Conclusion: These results suggest that subchondral bone resorption pits contribute to cartilage degradation by expressing matrix metalloproteinases in OA.

MeSH terms

  • Aged
  • Bone Marrow Cells / enzymology*
  • Bone Morphogenetic Proteins / analysis
  • Bone Remodeling / physiology
  • Bone Resorption / metabolism
  • Bone Resorption / physiopathology*
  • Cadaver
  • Cartilage, Articular / blood supply
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / physiopathology
  • Collagenases / analysis
  • Humans
  • Immunohistochemistry / methods
  • Matrix Metalloproteinase 1 / analysis
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3 / analysis
  • Matrix Metalloproteinases / analysis*
  • Neovascularization, Pathologic / physiopathology
  • Osteoarthritis, Knee / metabolism
  • Osteoarthritis, Knee / physiopathology*
  • Proteoglycans / metabolism
  • Vimentin / analysis
  • Vitronectin / analysis

Substances

  • Bone Morphogenetic Proteins
  • Proteoglycans
  • Vimentin
  • Vitronectin
  • Collagenases
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 1