CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Activation of Shc1 Allows Oncostatin M to Induce RANKL and Osteoclast Formation More Effectively Than Leukemia Inhibitory Factor
Umeå University, Faculty of Medicine, Department of Odontology.
Show others and affiliations
2019 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 1164Article in journal (Refereed) Published
Abstract [en]

Background and Purpose: The gp130 family of cytokines signals through receptors dimerizing with the gp130 subunit. Downstream signaling typically activates STAT3 but also SHP2/Ras/MAPK pathways. Oncostatin M (OSM) is a unique cytokine in this family since the receptor (OSMR) activates a non-redundant signaling pathway by recruitment of the adapter Shc1. We have studied the functional relevance of Shc1 for OSM-induced bone resorption.

Experimental Approach: Osteoblasts were stimulated with OSM and STAT3 and Shc1 activations were studied using real-time PCR and Western blots. The role of STAT3 and Shc1 for OSM-induced RANKL expression and osteoclast formation was studied by silencing their mRNA expressions. Effects of OSM were compared to those of the closely related cytokine leukemia inhibitory factor (LIF).

Key Results: OSM, but not LIF, induced the mRNA and protein expression of Shc1 and activated phosphorylation of Shc1 in the osteoblasts. Silencing of Shc1 decreased OSM-induced activation of STAT3 and RANKL expression. Silencing of STAT3 had no effect on activation of Shc1, but prevented the OSM-mediated increase of RANKL expression. Silencing of either Shc1 or STAT3 in osteoblasts decreased formation of osteoclasts in OSM-stimulated co-cultures of osteoblasts and macrophages. In agreement with these observations, OSM was a more potent and robust stimulator than LIF of RANKL formation and bone resorption in mouse calvariae and osteoclast formation in bone marrow cultures.

Conclusions and Implications: Activation of the Shc1-dependent STAT3 signaling is crucial for OSM-induced osteoclast formation. Inhibition of Shc1 is a potential mechanism to specifically inhibit OSM-induced bone resorption.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019. Vol. 10, article id 1164
Keywords [en]
OSM, LIF, RANKL, Shc1, osteoclast, bone resorption
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:umu:diva-159851DOI: 10.3389/fimmu.2019.01164ISI: 000469268500001OAI: oai:DiVA.org:umu-159851DiVA, id: diva2:1322981
Funder
Swedish Research CouncilSwedish Rheumatism AssociationKing Gustaf V Jubilee FundVästerbotten County CouncilAvailable from: 2019-06-11 Created: 2019-06-11 Last updated: 2019-06-11Bibliographically approved

Open Access in DiVA

fulltext(8967 kB)24 downloads
File information
File name FULLTEXT01.pdfFile size 8967 kBChecksum SHA-512
a86c133d1abf0cc0c43e265d7b842041677f4e72f2b5ac274b010371a81fa6481b0ae8f3e47c810b829ed725d2245039d11d79c34121e107c095ab39015207b5
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Persson, EmmaLerner, Ulf H.
By organisation
Department of Odontology
In the same journal
Frontiers in Immunology
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 24 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 45 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf