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Bone resorptive activity of human peripheral blood mononuclear cells after fusion with polyethylene glycol

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Abstract

The bone remodeling process occurs through bone formation by osteoblasts and bone resorption by osteoclasts, a process involving the contribution of endocrine and nervous systems. The mechanisms associated to differentiation and proliferation of osteoclasts and osteoblasts are considered a potential therapeutic target for treating some erosive bone diseases. The aim of the present study is to explore the feasibility of generating active osteoclast-like cells from peripheral blood mononuclear cells (PBMCs) following polyethylene glycol (PEG)-induced fusion. PEG-fused PBMCs showed TRAP+-multinucleated cells and bone resorption activity, and were also positive for osteoclast markers such as carbonic anhydrase II, calcitonin receptor, vacuolar ATPase, and cathepsin K, when examined by reverse transcription-polymerase chain reaction, immunochemistry and Western blotting. TRAP expression and bone resorptive activity were higher in whole PEG-fused PBMCs than in separated T lymphocytes, B lymphocytes or monocytes. Both TRAP expression and bone resorptive activity were also higher in osteogenesis imperfecta patients compared to PEG-fused PBMCs from healthy individuals. PEG-induced fusion was more efficient in inducing TRAP and bone resorptive activities than macrophage colony-stimulating factor or dexamethasone treatment. Bone resorptive activity of PEG-fused PMBCs was inhibited by bisphosphonates. Evidence is provided that the use of PEG-based cell fusion is a straightforward and amenable method for studying human osteoclast differentiation and testing new therapeutic strategies.

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Authors and Affiliations

  1. Departamento de Ciencias Fisiológicas, Facultad de Medicina, Universidad Nacional de Colombia, Carrera 30 No. 45-03, Bogotá, Colombia

    Edwin Manrique, Luz M. Castillo, Carlos A. Guerrero & Orlando Acosta

  2. Departamento de Ortopedia, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia

    Oswaldo Lazala

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  1. Edwin Manrique
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  2. Luz M. Castillo
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  3. Oswaldo Lazala
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  4. Carlos A. Guerrero
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  5. Orlando Acosta
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Correspondence to Carlos A. Guerrero.

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Edwin Manrique, Luz M. Castillo, Oswaldo Lazala, Carlos A. Guerrero, Orlando Acosta declare that they have no conflict of interest.

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Manrique, E., Castillo, L.M., Lazala, O. et al. Bone resorptive activity of human peripheral blood mononuclear cells after fusion with polyethylene glycol. J Bone Miner Metab 35, 127–141 (2017). https://doi.org/10.1007/s00774-016-0744-0

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  • DOI: https://doi.org/10.1007/s00774-016-0744-0

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