Tags

Type your tag names separated by a space and hit enter

TRP14 inhibits osteoclast differentiation via its catalytic activity.
Mol Cell Biol. 2014 Sep 15; 34(18):3515-24.MC

Abstract

We previously reported the inhibitory role of thioredoxin-related protein of 14 kDa (TRP14), a novel disulfide reductase, in nuclear factor-κB (NF-κB) activation, but its biological function has remained to be explored. Here, we evaluated the role of TRP14 in the differentiation and function of osteoclasts (OCs), for which NF-κB and cellular redox regulation have been known to be crucial, using RAW 264.7 macrophage cells expressing wild-type TRP14 or a catalytically inactive mutant, as well as its small interfering RNA. TRP14 depletion enhanced OC differentiation, actin ring formation, and bone resorption, as well as the accumulation of reactive oxygen species (ROS). TRP14 depletion promoted the activation of NF-κB, c-Jun NH2-terminal kinase, and p38, the expression of c-Fos, and the consequent induction of nuclear factor of activated T cell, cytoplasmic 1 (NFATc1), a key determinant of osteoclastogenesis. However, pretreatment with N-acetylcysteine or diphenylene iodonium significantly reduced the OC differentiation, as well as the ROS accumulation and NF-κB activation, that were enhanced by TRP14 depletion. Furthermore, receptor activator of NF-κB ligand (RANKL)-induced ROS accumulation, NF-κB activation, and OC differentiation were inhibited by the ectopic expression of wild-type TRP14 but not by its catalytically inactive mutant. These results suggest that TRP14 regulates OC differentiation and bone resorption through its catalytic activity and that enhancing TRP14 may present a new strategy for preventing bone resorption diseases.

Authors+Show Affiliations

Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, Republic of Korea.Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, Republic of Korea.Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, Republic of Korea.Department of Molecular Biology, College of Natural Science, Sejong University, Seoul, Republic of Korea.Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, Republic of Korea jeongw@ewha.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25002534

Citation

Hong, Sohyun, et al. "TRP14 Inhibits Osteoclast Differentiation Via Its Catalytic Activity." Molecular and Cellular Biology, vol. 34, no. 18, 2014, pp. 3515-24.
Hong S, Huh JE, Lee SY, et al. TRP14 inhibits osteoclast differentiation via its catalytic activity. Mol Cell Biol. 2014;34(18):3515-24.
Hong, S., Huh, J. E., Lee, S. Y., Shim, J. K., Rhee, S. G., & Jeong, W. (2014). TRP14 inhibits osteoclast differentiation via its catalytic activity. Molecular and Cellular Biology, 34(18), 3515-24. https://doi.org/10.1128/MCB.00293-14
Hong S, et al. TRP14 Inhibits Osteoclast Differentiation Via Its Catalytic Activity. Mol Cell Biol. 2014 Sep 15;34(18):3515-24. PubMed PMID: 25002534.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TRP14 inhibits osteoclast differentiation via its catalytic activity. AU - Hong,Sohyun, AU - Huh,Jeong-Eun, AU - Lee,Soo Young, AU - Shim,Jae-Kyung, AU - Rhee,Sue Goo, AU - Jeong,Woojin, Y1 - 2014/07/07/ PY - 2014/7/9/entrez PY - 2014/7/9/pubmed PY - 2014/10/18/medline SP - 3515 EP - 24 JF - Molecular and cellular biology JO - Mol. Cell. Biol. VL - 34 IS - 18 N2 - We previously reported the inhibitory role of thioredoxin-related protein of 14 kDa (TRP14), a novel disulfide reductase, in nuclear factor-κB (NF-κB) activation, but its biological function has remained to be explored. Here, we evaluated the role of TRP14 in the differentiation and function of osteoclasts (OCs), for which NF-κB and cellular redox regulation have been known to be crucial, using RAW 264.7 macrophage cells expressing wild-type TRP14 or a catalytically inactive mutant, as well as its small interfering RNA. TRP14 depletion enhanced OC differentiation, actin ring formation, and bone resorption, as well as the accumulation of reactive oxygen species (ROS). TRP14 depletion promoted the activation of NF-κB, c-Jun NH2-terminal kinase, and p38, the expression of c-Fos, and the consequent induction of nuclear factor of activated T cell, cytoplasmic 1 (NFATc1), a key determinant of osteoclastogenesis. However, pretreatment with N-acetylcysteine or diphenylene iodonium significantly reduced the OC differentiation, as well as the ROS accumulation and NF-κB activation, that were enhanced by TRP14 depletion. Furthermore, receptor activator of NF-κB ligand (RANKL)-induced ROS accumulation, NF-κB activation, and OC differentiation were inhibited by the ectopic expression of wild-type TRP14 but not by its catalytically inactive mutant. These results suggest that TRP14 regulates OC differentiation and bone resorption through its catalytic activity and that enhancing TRP14 may present a new strategy for preventing bone resorption diseases. SN - 1098-5549 UR - https://www.unboundmedicine.com/medline/citation/25002534/TRP14_inhibits_osteoclast_differentiation_via_its_catalytic_activity_ L2 - http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=25002534 DB - PRIME DP - Unbound Medicine ER -