PMID- 23124514 OWN - NLM STAT- MEDLINE DCOM- 20130411 LR - 20131121 IS - 1529-0131 (Electronic) IS - 0004-3591 (Linking) VI - 65 IP - 2 DP - 2013 Feb TI - Interleukin-17A stimulates granulocyte-macrophage colony-stimulating factor release by murine osteoblasts in the presence of 1,25-dihydroxyvitamin D(3) and inhibits murine osteoclast development in vitro. PG - 436-46 LID - 10.1002/art.37762 [doi] AB - OBJECTIVE: To investigate the effects of interleukin-17A (IL-17A) on osteoclastogenesis in vitro. METHODS: 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(-/-)) mice. Monocultures of BMCs or cocultures of BMCs and osteoblasts were supplemented with or without 1,25-dihydroxyvitamin D(3)(1,25[OH](2)D(3)), 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. RESULTS: In both culture systems, IL-17A alone did not affect the development of osteoclasts. However, the addition of IL-17A plus 1,25(OH)(2)D(3) 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(-/-) 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. CONCLUSION: These findings suggest that IL-17A interferes with the differentiation of osteoclast precursors by inducing the release of GM-CSF from osteoblasts. CI - Copyright (c) 2013 by the American College of Rheumatology. FAU - Balani, Deepak AU - Balani D AD - Bern University Hospital and University of Bern, Bern, Switzerland. FAU - Aeberli, Daniel AU - Aeberli D FAU - Hofstetter, Willy AU - Hofstetter W FAU - Seitz, Michael AU - Seitz M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 RN - 0 (Interleukin-17) RN - 0 (Osteoprotegerin) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - FXC9231JVH (Calcitriol) SB - IM MH - Animals MH - Calcitriol/*pharmacology MH - Cell Count MH - Cell Differentiation/drug effects/*physiology MH - Cells, Cultured MH - Granulocyte-Macrophage Colony-Stimulating Factor/*metabolism MH - Interleukin-17/*pharmacology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Osteoblasts/cytology/drug effects/*metabolism MH - Osteoclasts/cytology/drug effects/*metabolism MH - Osteoprotegerin/metabolism EDAT- 2012/11/06 06:00 MHDA- 2013/04/12 06:00 CRDT- 2012/11/06 06:00 PHST- 2012/03/14 00:00 [received] PHST- 2012/10/16 00:00 [accepted] PHST- 2012/11/06 06:00 [entrez] PHST- 2012/11/06 06:00 [pubmed] PHST- 2013/04/12 06:00 [medline] AID - 10.1002/art.37762 [doi] PST - ppublish SO - Arthritis Rheum. 2013 Feb;65(2):436-46. doi: 10.1002/art.37762.