title: Enhanced osteolytic potential of monocytes/macrophages derived from bone marrow after particle stimulation.
abstract: BACKGROUND
  Total hip replacement can be complicated by periprosthetic osteolysis. Monocytes/macrophages play a major role in the formation of the foreign body granulomas induced by wear debris. We hypothesized that periprosthetic monocytes/macrophages do not only accelerate inflammatory and osteoclast-mediated osteolytic processes, but also resorb periprosthetic bone directly by themselves. This study was designed to evaluate the osteolytic potential in vitro of monocytes/macrophages derived from bone marrow.
  
  
  METHODS
  Monocytes/macrophages were produced by filtration of rat bone marrow cells, followed by culture in the presence of macrophage-colony stimulating factor (M-CSF). Monocyte/macrophage properties were ascertained using immunocytochemistry and phagocytic activity. Osteolytic cytokines and extracellular matrix degrading proteinases were quantified at the mRNA level.
  
  
  RESULTS
  Adherent cell fraction was immunoreactive for the monocyte/macrophage specific marker CD68 and active in the phagocytosis of carbon particles up to 72 h. They also showed immunoreactivity to cathepsin K, IL-1beta, IL-6, and M-CSF, but mostly did not react to TRAP. mRNA levels of osteolytic cytokines and extracellular matrix degrading proteinases were enhanced, but that of RANKL were not. Monocytes/macrophages resorbed dentine discs and carbonated calcium phosphate was very actively resorbed after stimulation with titanium particles.
  
  
  CONCLUSIONS
  Harvested bone marrow cells expressed monocyte/macrophage phenotype, but not osteoclastic markers. The capacity of these cathepsin-K-positive phagocytic cells to resorb dentine discs and carbonated calcium phosphate in vitro suggests a direct role of monocytes/macrophages in bone resorption and periprosthetic osteolysis. The finding supports our hypothesis and previous histomorphometric observations on the presence of such osteolytic macrophages in vivo around loosening prosthesis.
authors.affiliation: Department of Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata 990-9585, Japan. ytamaki@med.id.yamagata-u.ac.jp
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Kan
authors.initials: K
authors.lastname: Sasaki
authors.forename: Akiko
authors.initials: A
authors.lastname: Sasaki
authors.forename: Yuya
authors.initials: Y
authors.lastname: Takakubo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ogino
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: Jari
authors.initials: J
authors.lastname: Salo
authors.forename: Michiaki
authors.initials: M
authors.lastname: Takagi
mesh_terms: D000135:Acid Phosphatase / Q000737:chemistry; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D001862:Bone Resorption / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D003804:Dentin / Q000473:pathology; D005269:Femur / Q000473:pathology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000737:chemistry; D008264:Macrophages / Q000473:pathology*; D009000:Monocytes / Q000473:pathology*; D010014:Osteolysis / Q000473:pathology*; D010587:Phagocytosis / Q000502:physiology; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013499:Surface Properties; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D007527:Isoenzymes; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase