title: Effects of soluble cobalt and cobalt incorporated into calcium phosphate layers on osteoclast differentiation and activation.
abstract: Metal ions originating from mechanical debris and corrosive wear of prosthetic implant alloys accumulate in peri-implant soft tissues, bone mineral, and body fluids. Eventually, metal ions such as cobalt (II) (Co(2+)), which is a major component of cobalt-chromium-based implant alloys and a known activator of osteolysis, are incorporated into the mineral phase of bone. We hypothesize that the accumulation of Co(2+) in the mineral could directly activate osteolysis by targeting osteoclasts. To test this hypothesis, we coated tissue culture plastic with a thin layer of calcium phosphate (CaP) containing added traces of Co(2+), thereby mimicking the bone mineral accumulation of Co(2+). Murine bone marrow osteoclasts formed in the presence of M-CSF and RANKL were cultured on these surfaces to examine the effects of Co(2+) on osteoclast formation and resorptive activity. Treatment conditions with Co(2+) involved incorporation into the CaP layer, adsorption to the mineral surface, or addition to culture media. Micromolar concentrations of Co(2+) delivered to developing osteoclast precursors by all 3 routes increased both osteoclast differentiation and resorptive function. Compared to CaP layers without Co(2+), we observed a maximal 75% increase in osteoclast numbers and a 2.3- to 2.7-fold increase in mineral resorption from the tissue culture wells containing 0.1 microM Co(2+) and 0.1-10 microM Co(2+), respectively. These concentrations are well within the range found in peri-implant tissues in vivo. This direct effect of Co(2+) on osteoclasts appears to act independently of the particulate phagocytosis/inflammation-mediated pathways, thus enhancing osteolysis and aseptic implant loosening.
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA. somying_patntirapong@student.hms.harvard.edu
authors.forename: Somying
authors.initials: S
authors.lastname: Patntirapong
authors.forename: Pamela
authors.initials: P
authors.lastname: Habibovic
authors.forename: Peter V
authors.initials: PV
authors.lastname: Hauschka
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002130:Calcium Phosphates / Q000494:pharmacology*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D020099:Coated Materials, Biocompatible / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D012995:Solubility / Q000187:drug effects; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D007527:Isoenzymes; D003035:Cobalt; C020243:calcium phosphate; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase