Transglutaminase 2 regulates osteoclast differentiation via aBlimp1-dependent pathway

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/486448.do
DOI
10.1038/s41598-017-11246-5
Title
Transglutaminase 2 regulates osteoclast differentiation via aBlimp1-dependent pathway
Description
This work was supported by a grant from the National Research Foundationof Korea (NRF-2014R1A2A1A10050406) to Hong-Hee Kim (Seoul NationalUniversity) and by a grant from the National Research Foundation ofKorea (NRF-2017R1D1A1B03028003) to Haemin Kim (Seoul NationalUniversity).
abstract
Transglutaminase 2 (TG2) performs multiple reactions, including transamidation, and also plays a role in signal transduction as a GTP-binding protein. In this study, we reveal that TG2 controls osteoclast differentiation and bone homeostasis in mice. Osteoclasts specifically expressed the TG2 isoform among eight TG family members. Suppression in TG2 expression with siRNA led to increased osteoclast formation from primary mouse precursor cells in response to receptor activator of nuclear factor kappaB ligand (RANKL). This osteoclastogenic effect of TG2 knockdown was associated with enhanced induction of c-Fos and NFATc1 by RANKL. Moreover, TG2 knockdown up-regulated B lymphocyte-induced maturation protein 1 (Blimp1), which represses anti-osteoclastogenic genes, in a manner dependent on the NF-kappa B signaling pathway. To the contrary, TG2 overexpression inhibited osteoclast formation and the expression of osteoclastogenic genes. Consistent with these in vitro results, TG2 knockout mice exhibited lower trabecular bone mass and increased number of osteoclasts compared with wild-type mice. Taken together, our results provide strong evidence that TG2 plays an important role in bone metabolism by suppressing excessive osteoclastogenesis via the regulation of the NF-kappa B-Blimp1 signaling pathway.
provenance
Made available in Cube on 2018-09-28T16:07:54Z (GMT). No. of bitstreams: 0
language
English
author
Kim, Woo-Shin
Kim, Haemin
Jeong, Eui Man
Kim, Hyung Joon
Lee, Zang Hee
Kim, In-Gyu
Kim, Hong-Hee
orcid
Jeong, Eui Man/0000-0003-0692-2033
accessioned
2018-09-28T16:07:54Z
available
2018-09-28T16:07:54Z
issued
2017
citation
SCIENTIFIC REPORTS(7)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/486448.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345274454
Jurisdiction
Rep.of Korea
Project Name
Center for Professional Education on Technosciences of Oral Health
rights
openAccess
type
article


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