title: Milk-Derived Nanoparticle Fraction Promotes the Formation of Small Osteoclasts But Reduces Bone Resorption.
abstract: The general consensus is that milk promotes bone growth and density because is a source of calcium and contains components that enhance intestinal calcium uptake or directly affect bone metabolism. In this study, we investigated the effect of bovine-derived milk 100,000 g pellet (P100), which contains nanoparticles (<220 nm) including extracellular vesicles, on osteoclast differentiation and bone resorption. Bone marrow-derived osteoclast precursor cells were differentiated into osteoclasts by M-CSF and RANKL (control) and in the presence of milk P100. Milk P100 treatment until day 4 increased the number of TRAP-positive mononuclear cells and small (≤5 nuclei) osteoclasts. The number of large (≥6 nuclei) osteoclasts remained the same. These alterations were associated with increased expression of TRAP, NFATc1, and c-Fos. Cells seeded in a calcium-phosphate coated plate or bone slices showed reduced resorption area when exposed to milk P100 during the differentiation phase and even after osteoclast formation. Interestingly, milk P100 treatment enhanced Cathepsin K expression but reduced Carbonic Anhydrase 2 gene expression. Moreover, intracellular acid production was also decreased by milk P100 treatment. Oral delivery of milk P100 to female DBA1/J mice for 7 weeks did not alter bone area; however, increased osteoclast number and area in tibia without changes in serum RANKL and CTX-I levels. We showed for the first time the effect of milk P100 on osteoclast differentiation both in vitro and in vivo and found that milk P100 increased the formation of small osteoclasts but this does not lead to more bone resorption probably due to reduced acid secretion. J. Cell. Physiol. 232: 225-233, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Marina C
authors.initials: MC
authors.lastname: Oliveira
authors.affiliation: Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Irene
authors.initials: I
authors.lastname: Di Ceglie
authors.affiliation: Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Onno J
authors.initials: OJ
authors.lastname: Arntz
authors.affiliation: Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
authors.affiliation: Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Frank H J
authors.initials: FH
authors.lastname: van den Hoogen
authors.affiliation: Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Adaliene V M
authors.initials: AV
authors.lastname: Ferreira
authors.affiliation: Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Peter L E M
authors.initials: PL
authors.lastname: van Lent
authors.affiliation: Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. fons.vandeloo@radboudumc.nl.
authors.forename: Fons A J
authors.initials: FA
authors.lastname: van de Loo
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy* / Q000378:metabolism; D002130:Calcium Phosphates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D008810:Mice, Inbred C57BL; D008892:Milk / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002130:Calcium Phosphates; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; C020243:calcium phosphate