PMID- 28343338 OWN - NLM STAT- MEDLINE DCOM- 20180202 LR - 20181202 IS - 1567-2387 (Electronic) IS - 1567-2379 (Linking) VI - 48 IP - 3 DP - 2017 Jun TI - Expression of typical osteoclast markers by PBMCs after PEG-induced fusion as a model for studying osteoclast differentiation. PG - 169-185 LID - 10.1007/s10735-017-9717-4 [doi] AB - Bone is a metabolically active organ subjected to continuous remodeling process that involves resorption by osteoclast and subsequent formation by osteoblasts. Osteoclast involvement in this physiological event is regulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappaB ligand (RANKL). Fusion of mono-nuclear pre-osteoclasts is a critical event for osteoclast differentiation and for bone resorption. Here we show that PBMCs can be successfully fused with polyethylenglicol (PEG) in order to generated viable osteoclast-like cells that exhibit tartrate-resistant acid phosphatase (TRAP) and bone resorptive activities. PEG-fused PBMCs expressed additional markers compatible with osteoclastogenic differentiation such as carbonic anhydrase II (CAII), calcitonin receptor (CR), cathepsin K (Cat K), vacuolar ATPase (V-ATPase) subunit C1 (V-ATPase), integrin beta3, RANK and cell surface aminopeptidase N/CD13. Actin redistribution in PEG-fused cells was found to be affected by cell cycle synchronization at G0/G1 or G2/M phases. PEG-induced fusion also led to expression of tyrosine kinases c-Src and Syk in their phosphorylated state. Scanning electron microscopy images showed morphological features typical of osteoclast-like cells. The results here shown allow concluding that PEG-induced fusion of PBMCs provides a suitable model system for understanding the mechanisms involved in osteoclastogenesis and for assaying new therapeutic strategies. FAU - Castillo, Luz M AU - Castillo LM AD - Departamento de Ciencias Fisiologicas, Facultad de Medicina, Universidad Nacional de Colombia, Bogota, Colombia. FAU - Guerrero, Carlos A AU - Guerrero CA AD - Departamento de Ciencias Fisiologicas, Facultad de Medicina, Universidad Nacional de Colombia, Bogota, Colombia. caguerrerof@unal.edu.co. FAU - Acosta, Orlando AU - Acosta O AD - Departamento de Ciencias Fisiologicas, Facultad de Medicina, Universidad Nacional de Colombia, Bogota, Colombia. LA - eng PT - Journal Article DEP - 20170325 PL - Netherlands TA - J Mol Histol JT - Journal of molecular histology JID - 101193653 RN - 0 (Biomarkers) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - EC 3.1.3.2 (ACP5 protein, human) RN - EC 3.1.3.2 (Tartrate-Resistant Acid Phosphatase) SB - IM MH - Biomarkers/analysis/blood MH - Bone Resorption MH - *Cell Differentiation MH - *Cell Fusion MH - Cells, Cultured MH - Humans MH - Leukocytes, Mononuclear/cytology/*metabolism MH - Models, Biological MH - Osteoclasts/*cytology MH - Polyethylene Glycols MH - Tartrate-Resistant Acid Phosphatase/metabolism OTO - NOTNLM OT - Bone resorption OT - Osteoclast activity OT - Osteoclast differentiation OT - Peripheral blood mononuclear cells OT - Polyethylenglicol EDAT- 2017/03/28 06:00 MHDA- 2018/02/03 06:00 CRDT- 2017/03/27 06:00 PHST- 2016/11/17 00:00 [received] PHST- 2017/03/20 00:00 [accepted] PHST- 2017/03/28 06:00 [pubmed] PHST- 2018/02/03 06:00 [medline] PHST- 2017/03/27 06:00 [entrez] AID - 10.1007/s10735-017-9717-4 [pii] AID - 10.1007/s10735-017-9717-4 [doi] PST - ppublish SO - J Mol Histol. 2017 Jun;48(3):169-185. doi: 10.1007/s10735-017-9717-4. Epub 2017 Mar 25.