RRC ID 39015
著者 Wakikawa T, Shioi A, Hino M, Inaba M, Nishizawa Y, Tatsumi N, Morii H, Otani S.
タイトル Thrombopoietin inhibits in vitro osteoclastogenesis from murine bone marrow cells.
ジャーナル Endocrinology
Abstract To determine whether thrombopoietin (TPO) can modulate the osteoclastic differentiation from hematopoietic stem cells, we investigated the effect of TPO on in vitro osteoclastogenesis by using the coculture of murine bone marrow cells with the stromal cell line (ST2) in the presence of 1alpha,25-dihydroxyvitamin D3 and dexamethasone. Recombinant human TPO inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated cells in a dose-dependent manner (0.02-200 ng/ml). The effect of TPO on differentiation of bone-resorbing capacity was investigated by pit assay. TPO dose dependently decreased the areas oftoluidine blue-stained resorption pits (2.0-200 ng/ml). To identify the cellular target of TPO, we used a variety of bone marrow/stromal cell coculture methods. Initially, we found that TPO mainly exerted its effect on the early stage of osteoclastic differentiation in delayed addition experiments. Consequently, the majority of TPO's inhibition of osteoclastic cell formation was due to its effect on bone marrow cells. Finally, we examined whether transforming growth factor-beta (TGFbeta) and platelet-derived growth factor (PDGF), major cytokines produced by megakaryocytes, mediate the inhibitory effect of TPO. The addition of either anti-TGFbeta or anti-PDGF antibody to bone marrow cell culture completely antagonized the effect of TPO on osteoclastogenesis. Furthermore, treatment of bone marrow cells with TGFbeta or PDGF mimicked the inhibitory effect of TPO. These data suggest that TPO inhibits osteoclastogenesis through stimulating thrombopoiesis and that TGFbeta and PDGF mediate the effect of TPO by impacting on macrophage-lineage cells as osteoclast precursors.
巻・号 138(10)
ページ 4160-6
公開日 1997-10-1
DOI 10.1210/endo.138.10.5438
PMID 9322925
MeSH Analysis of Variance Animals Bone Marrow / drug effects Bone Marrow Cells* Calcitriol / pharmacology Cell Differentiation / drug effects Cell Line Cells, Cultured Coculture Techniques Cytokines / metabolism Dexamethasone / pharmacology Dose-Response Relationship, Drug Hematopoietic Stem Cells / cytology Histocytochemistry Humans Image Processing, Computer-Assisted Macrophages / cytology Macrophages / drug effects Megakaryocytes / drug effects Mice Mice, Inbred C3H Osteoclasts / cytology* Osteoclasts / drug effects Platelet-Derived Growth Factor / pharmacology Stromal Cells / cytology Stromal Cells / drug effects Thrombopoietin / pharmacology* Transforming Growth Factor alpha / pharmacology
IF 3.934
引用数 19
WOS 分野 ENDOCRINOLOGY & METABOLISM
リソース情報
ヒト・動物細胞 ST2(RCB0224)