Interleukin‐17A stimulates granulocyte–macrophage colony‐stimulating factor release by murine osteoblasts in the presence of 1, 25‐dihydroxyvitamin D3 and inhibits murine osteoclast development in vitro. Issue 2 (28th January 2013)

• Record Type: Journal Article
• Authors: Balani, Deepak; Aeberli, Daniel; Hofstetter, Willy; Seitz, Michael
• Is Part Of: Arthritis and rheumatism. Volume 65:Issue 2(2013:Feb.)
• Page Start: 436
• Page End: 446
• Publication Date: 2013-01-28
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; Arthritis -- Periodicals; Rheumatic Diseases -- Periodicals; Rhumatisme -- Périodiques; Arthrite -- Périodiques; 616.72
• DOI: 10.1002/art.37762
• Languages: English
• ISSNs: 0004-3591

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="abs1-1" sec-type="section"> <title>Objective</title> <p>To investigate the effects of interleukin‐17A (IL‐17A) on osteoclastogenesis in vitro.</p> </sec> <sec id="abs1-2" sec-type="section"> <title>Methods</title> <p>Bone marrow cells (BMCs) were isolated from the excised tibia and femora of wild‐type C57BL/6J mice, and osteoblasts were obtained by sequential digestion of the calvariae of ddY, C57BL/6J, and granulocyte–macrophage colony‐stimulating factor–knockout (GM‐CSF<sup>−/−</sup>) mice. Monocultures of BMCs or cocultures of BMCs and osteoblasts were supplemented with or without 1, 25‐dihydroxyvitamin D<sub>3</sub> (1, 25[OH]<sub>2</sub>D<sub>3</sub>), recombinant human macrophage colony‐stimulating factor (M‐CSF), RANKL, and IL‐17A. After 5–6 days, the cultures were fixed with 4% paraformaldehyde and subsequently stained for the osteoclast marker enzyme tartrate‐resistant acid phosphatase (TRAP). Osteoprotegerin (OPG) and GM‐CSF expression were measured by enzyme‐linked immunosorbent assay, and transcripts for RANK and RANKL were detected by real‐time polymerase chain reaction.</p> </sec> <sec id="abs1-3" sec-type="section"> <title>Results</title> <p>In both culture systems, IL‐17A alone did not affect the development of osteoclasts. However, the addition of IL‐17A plus 1, 25(OH)<sub>2</sub>D<sub>3</sub> to cocultures inhibited early osteoclast development within the first 3 days of culture and induced release of GM‐CSF into the culture supernatants. Furthermore, in cocultures of GM‐CSF<sup>−/−</sup> mouse osteoblasts and wild‐type mouse BMCs, IL‐17A did not affect osteoclast development, corroborating the role of GM‐CSF as the mediator of the observed inhibition of osteoclastogenesis by IL‐17A.</p> </sec> <sec id="abs1-4" sec-type="section"> <title>Conclusion</title> <p>These findings suggest that IL‐17A interferes with the differentiation of osteoclast precursors by inducing the release of GM‐CSF from osteoblasts.</p> </sec> </abstract>