title: IL-17A suppresses the expression of bone resorption-related proteinases and osteoclast differentiation via IL-17RA or IL-17RC receptors in RAW264.7 cells.
abstract: Interleukin-17 (IL-17) is produced exclusively by activated T cells and neutrophils, and stimulates osteoclastic bone resorption via osteoblasts by inducing the expression of "receptor activator of NF-kappaB (RANK) ligand" (RANKL). However, the direct effects of IL-17 on the differentiation of osteoclast precursors into osteoclasts and on the function of osteoclasts have not been clarified. Therefore, we examined the effects of IL-17A on the differentiation of osteoclast precursors using RAW264.7 cells and also on the expression of carbonic anhydrase II (CA II), cathepsin K, matrix metalloproteinases-9 (MMP-9), RANK, c-fms, and IL-17 receptors in these cells. The cells were cultured with or without 0.1, 1.0, 10 or 50 ng/mL IL-17 in the presence of soluble RANKL for up to 10 days. The CA II, cathepsin K, and MMP-9 mRNA and protein expression levels were examined using real-time PCR and Western blotting, respectively. The mRNA expression levels of RANK, c-fms, and IL-17 receptors were monitored by real-time PCR. Osteoclast differentiation was estimated using tartrate-resistant acid phosphatase (TRAP) staining of the cells. TRAP-positive cells were observed after day 5 of culture, and the number of cells decreased in the presence of 10 and 50 ng/mL IL-17A at days 5 and 7. In the presence of IL-17A, the expressions of cathepsin K, MMP-9 and c-fms decreased markedly on days 5 and/or 7 of culture, whereas the expression of CA II and IL-17 receptor (type A) increased remarkably at days 3 and 7, respectively. The expression of RANK and IL-17 receptor (type C) was not affected by the addition of IL-17A. These results suggest that the differentiation of osteoclast precursors into osteoclasts is suppressed at high concentrations of IL-17A. Furthermore, IL-17A suppresses the hydrolysis of matrix proteins during bone resorption by decreasing the production of cathepsin K and MMP-9 in osteoclasts.
authors.affiliation: Department of Oral Health Sciences, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kitami
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kawato
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tanabe
authors.forename: Tomoko
authors.initials: T
authors.lastname: Katono-Tani
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Naoto
authors.initials: N
authors.lastname: Suzuki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yonehara
authors.forename: Masao
authors.initials: M
authors.lastname: Maeno
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000235:genetics; D024402:Carbonic Anhydrase II / Q000096:biosynthesis; D056657:Cathepsin K / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D020381:Interleukin-17 / Q000235:genetics / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000096:biosynthesis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D053722:Receptors, Interleukin-17 / Q000096:biosynthesis / Q000502:physiology*; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D020381:Interleukin-17; D007527:Isoenzymes; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D053722:Receptors, Interleukin-17; C505687:Tnfrsf11a protein, mouse; D016186:Receptor, Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; D020780:Matrix Metalloproteinase 9; D024402:Carbonic Anhydrase II