Endogenous production of TGF-beta is essential for osteoclastogenesis induced by a combination of receptor activator of NF-kappa B ligand and macrophage-colony-stimulating factor
In: Journal of immunology (Baltimore, Md. : 1950), Jg. 165 (2000-10-18), Heft 8
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Zugriff:
Differentiation of osteoclasts, the cells primarily responsible for bone resorption, is controlled by a variety of osteotropic hormones and cytokines. Of these factors, receptor activator of NF-κB (RANK) ligand (RANKL) has been recently cloned as an essential inducer of osteoclastogenesis in the presence of M-CSF. Here, we isolated a stroma-free population of monocyte/macrophage (M/Mφ)-like hemopoietic cells from mouse unfractionated bone cells that were capable of differentiating into mature osteoclasts by treatment with soluble RANKL (sRANKL) and M-CSF. However, the efficiency of osteoclast formation was low, suggesting the requirement for additional factors. The isolated M/Mφ-like hemopoietic cells expressed TGF-β and type I and II receptors of TGF-β. Therefore, we examined the effect of TGF-β on osteoclastogenesis. TGF-β with a combination of sRANKL and M-CSF promoted the differentiation of nearly all M/Mφ-like hemopoietic cells into cells of the osteoclast lineage. Neutralizing anti-TGF-β Ab abrogated the osteoclast generation. These TGF-β effects were also observed in cultures of unfractionated bone cells, and anti-TGF-β blocked the stimulatory effect of 1,25-dihydroxyvitamin D3. Translocation of NF-κB into nuclei induced by sRANKL in TGF-β-pretreated M/Mφ-like hemopoietic cells was greater than that in untreated cells, whereas TGF-β did not up-regulate the expression of RANK, the receptor of RANKL. Our findings suggest that TGF-β is an essential autocrine factor for osteoclastogenesis.
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Endogenous production of TGF-beta is essential for osteoclastogenesis induced by a combination of receptor activator of NF-kappa B ligand and macrophage-colony-stimulating factor
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Autor/in / Beteiligte Person: | Sato, Takuya ; Nakagawa, Mari ; Ogasawara, Aichi ; Hakeda, Yoshiyuki ; Kaneko, Hironori ; Kumegawa, Masayoshi ; Mano, Hiroshi ; Nojima, Takaki ; Kaneda, Toshio |
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Zeitschrift: | Journal of immunology (Baltimore, Md. : 1950), Jg. 165 (2000-10-18), Heft 8 |
Veröffentlichung: | 2000 |
Medientyp: | unknown |
ISSN: | 0022-1767 (print) |
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