Different Blood-Borne Human Osteoclast Precursors Respond in Distinct Ways to IL-17A.
Osteoclasts are bone-degrading cells that are formed through fusion of their monocytic precursors. Three distinct subsets of monocytes have been identified in human peripheral blood: classical, intermediate, and non-classical monocytes. They are known to play different roles in physiology and pathology, but their capacity to differentiate into osteoclasts and whether inflammatory cytokines influence this differentiation is unknown. We hypothesized that classical, intermediate, and non-classical monocytes generate functionally different osteoclasts and that they respond in different ways to the inflammatory cytokine interleukin-17A (IL-17A). To investigate this, the different monocyte subsets were isolated from human peripheral blood and osteoclastogenesis was induced with the cytokines M-CSF and RANKL, with or without IL-17A. We found that all subsets are able to differentiate into osteoclasts in vitro, and that both osteoclastogenesis and subsequent bone resorption was distinctly affected by IL-17A. Osteoclastogenesis and bone resorption by osteoclasts derived from classical monocytes remained unaffected by IL-17A, while osteoclast formation from intermediate monocytes was inhibited by the cytokine. Surprisingly, bone resorption by osteoclasts derived from intermediate monocytes remained at similar levels as control cultures, indicating an increased bone resorbing activity by these osteoclasts. Limited numbers of osteoclasts were formed from non-classical monocytes on bone and no bone resorption was detected, which suggest that these cells belong to a cell lineage different from the osteoclast. By providing more insight into osteoclast formation from human blood monocytes, this study contributes to the possible targeting of specific osteoclast precursors as a therapeutic approach for diseases associated with inflammatory bone loss.
Department of Oral Cell Biology and Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Gustav Mahlerlaan, Amsterdam, The Netherlands.
Sara
S
Sprangers
Department of Oral Cell Biology and Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Gustav Mahlerlaan, Amsterdam, The Netherlands.|Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Gustav Mahlerlaan, Amsterdam, The Netherlands.
Ton
T
Schoenmaker
Department of Oral Cell Biology and Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Gustav Mahlerlaan, Amsterdam, The Netherlands.
Yixuan
Y
Cao
Department of Oral Cell Biology and Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Gustav Mahlerlaan, Amsterdam, The Netherlands.
Vincent
V
Everts
Department of Oral Cell Biology and Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Gustav Mahlerlaan, Amsterdam, The Netherlands.|Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Gustav Mahlerlaan, Amsterdam, The Netherlands.
Teun J
TJ
de Vries
D001862:Bone Resorption; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage; D002478:Cells, Cultured; D058851:GPI-Linked Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology; D017452:Receptors, IgG / Q000378:metabolism; D013997:Time Factors
C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; C508717:IL17A protein, human; D020381:Interleukin-17; D018950:Lipopolysaccharide Receptors; D053245:RANK Ligand; D017452:Receptors, IgG; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor