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http://purl.uniprot.org/citations/17002586http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17002586http://www.w3.org/2000/01/rdf-schema#comment"

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Enhanced osteoclastogenesis was observed in bone marrow-derived macrophage cells from 4-1BB-deficient mice than in those from wildtype mice. 4-1BB and 4-1BB ligand interaction may play a role at a certain stage of osteoclast formation through increased level of IL-10, a negative regulator of osteoclastogenesis.

Introduction

4-1BB is an inducible T-cell costimulatory molecule and a member of the TNF receptor family. The expression pattern of 4-1BB and 4-1BB ligand (4-1BBL) has suggested that 4-1BB plays a role not only in various responses related to innate immunity but also in bone metabolism.

Materials and methods

Osteoclast formation was evaluated in bone marrow-derived macrophage cells (BMMs) from wildtype and 4-1BB-deficient (4-1BB-/-) mice. Expression of interleukin-10 (IL-10) during osteoclast formation was analyzed at the mRNA and protein levels.

Results

Expression of IL-10 was higher in RANKL-stimulated wildtype BMMs than 4-1BB-/-BMMs. When 4-1BBL was stimulated with 4-1BB-Fc fusion protein, the expression of IL-10 in BMMs increased. Neutralization of IL-10 was not as effective in preventing inhibition by IL-10 of osteoclast differentiation in 4-1BB-/-BMMs as in wildtype BMMs. When IL-10 was added to the culture medium, osteoclast formation was inhibited more efficiently in the 4-1BB-/-BMMs than in the wildtype BMMs.

Conclusions

Interaction of 4-1BB and 4-1BBL stimulates IL-10 production through 4-1BBL signaling. 4-1BBL plays a role at a certain stage of osteoclast formation, and IL-10 may mediate this effect. The elevated level of osteoclastogenesis in 4-1BB-/-BMMs may thus be caused, in part, by a lower level of IL-10."xsd:string
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http://purl.uniprot.org/citations/17002586http://purl.uniprot.org/core/author"Lee J.E."xsd:string
http://purl.uniprot.org/citations/17002586http://purl.uniprot.org/core/author"Choi H.S."xsd:string
http://purl.uniprot.org/citations/17002586http://purl.uniprot.org/core/author"Lee E.A."xsd:string
http://purl.uniprot.org/citations/17002586http://purl.uniprot.org/core/author"Kwon B.S."xsd:string
http://purl.uniprot.org/citations/17002586http://purl.uniprot.org/core/author"Shin H.H."xsd:string
http://purl.uniprot.org/citations/17002586http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/17002586http://purl.uniprot.org/core/name"J Bone Miner Res"xsd:string
http://purl.uniprot.org/citations/17002586http://purl.uniprot.org/core/pages"1907-1912"xsd:string
http://purl.uniprot.org/citations/17002586http://purl.uniprot.org/core/title"Enhanced osteoclastogenesis in 4-1BB-deficient mice caused by reduced interleukin-10."xsd:string
http://purl.uniprot.org/citations/17002586http://purl.uniprot.org/core/volume"21"xsd:string
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