title: The tumor necrosis factor type 2 receptor plays a protective role in tumor necrosis factor-α-induced bone resorption lacunae on mouse calvariae.
abstract: Tumor necrosis factor (TNF)-α exerts its biological function via TNF type 1 and type 2 receptors (TNFR1 and TNFR2). We have previously reported that bone resorption induced by lipopolysaccharide (LPS) in TNFR2-deficient mice is accelerated compared to that in wild-type (WT) mice. Although these results suggested that TNFR2 might have a protective role in bone resorption, we could not exclude the possibility that TNFR2 has no role in bone resorption. To clarify the role of TNFR2, we developed a TNF-α-induced bone resorption model using cholesterol-bearing pullulan nanogel as a TNF-α carrier to minimize the influence of inflammatory cytokines other than TNF-α. Injections of human TNF-α (hTNF), an agonist of mouse TNFR1, stimulated bone resorption lacunae on the calvariae in WT mice, but mouse TNF-α (mTNF), an agonist of both mouse TNFR1 and TNFR2, could not. To eliminate the possibility that the TNFR1 agonistic effects of hTNF were stronger than those of mTNF, we used the same model in TNFR2-deficient mice. Injection of mTNF resulted in clear bone resorption lacunae to the same extent observed after using hTNF in the TNFR2-deficient mice. Histomorphometric analysis of osteoclast number supported the observed changes in bone resorption lacunae. These data suggest that TNFR2 has a protective role in TNF-α-induced bone resorption.
authors.affiliation: Section of Pharmacology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo 113-8549, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nagano
authors.forename: Neil
authors.initials: N
authors.lastname: Alles
authors.forename: Anower Hussain
authors.initials: AH
authors.lastname: Mian
authors.forename: Asako
authors.initials: A
authors.lastname: Shimoda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Morimoto
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Tamura
authors.forename: Hitoyata
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Kazunari
authors.initials: K
authors.lastname: Akiyoshi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ohya
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Aoki
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000235:genetics; D001862:Bone Resorption / Q000139:chemically induced* / Q000378:metabolism*; D005936:Glucans / Q000737:chemistry; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000819:agonists / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012886:Skull / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D005936:Glucans; D000080385:Nanogels; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; C009109:pullulan; D011094:Polyethyleneimine