Tags

Type your tag names separated by a space and hit enter

Regulation of human osteoclast differentiation by thioredoxin binding protein-2 and redox-sensitive signaling.
J Bone Miner Res. 2004 Dec; 19(12):2057-64.JB

Abstract

Differential expression of TBP-2 and Trx-1 occurs during osteoclastogenesis. Adenoviral overexpression of TBP-2 in osteoclast precursors inhibits Trx-1 expression, osteoclast formation, and AP-1 binding activity. TBP-2 and Trx-1 are key regulators of osteoclastogenesis.

INTRODUCTION

Thioredoxin binding protein-2 (TBP-2) negatively regulates thioredoxin-1 (Trx-1), a key endogenous modulator of cellular redox and signaling. In gene array analysis, we found that TBP-2 expression was reduced during human osteoclast differentiation compared with macrophage differentiation. Our aim was to determine the roles of TBP-2 and Trx-1 in human osteoclastogenesis and RANKL signaling.

MATERIALS AND METHODS

Osteoclasts or macrophages were generated from colony-forming unit-granulocyte macrophage (CFU-GM) precursors treated with sRANKL and macrophage-colony-stimulating factor (M-CSF), or M-CSF alone, respectively. Expression of TBP-2 and Trx-1 was quantified by real-time PCR and Western analysis. Adenoviral gene transfer was used to overexpress TBP-2 in precursors. NF-kappaB and activator protein 1 (AP-1) signaling was assessed with EMSA.

RESULTS

In the presence of sRANKL, expression of TBP-2 was decreased, whereas Trx-1 expression was increased. The antioxidant N-acetylcysteine reversed this pattern and markedly inhibited osteoclastogenesis. Adenoviral overexpression of human TBP-2 in precursors inhibited osteoclastogenesis and Trx-1 expression, inhibited sRANKL-induced DNA binding of AP-1, but enhanced sRANKL-induced DNA binding of NF-kappaB.

CONCLUSIONS

These data support significant roles for TBP-2 and the Trx system in osteoclast differentiation that are mediated by redox regulation of AP-1 transcription. A likely mechanism of stress signal induction of bone resorption is provided. Modulators of the Trx system such as antioxidants have potential as antiresorptive therapies.

Authors+Show Affiliations

Department of Clinical and Biomedical Sciences: Barwon Health, The University of Melbourne, Geelong, Victoria 3220, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15537450

Citation

Aitken, Cathy J., et al. "Regulation of Human Osteoclast Differentiation By Thioredoxin Binding Protein-2 and Redox-sensitive Signaling." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 19, no. 12, 2004, pp. 2057-64.
Aitken CJ, Hodge JM, Nishinaka Y, et al. Regulation of human osteoclast differentiation by thioredoxin binding protein-2 and redox-sensitive signaling. J Bone Miner Res. 2004;19(12):2057-64.
Aitken, C. J., Hodge, J. M., Nishinaka, Y., Vaughan, T., Yodoi, J., Day, C. J., Morrison, N. A., & Nicholson, G. C. (2004). Regulation of human osteoclast differentiation by thioredoxin binding protein-2 and redox-sensitive signaling. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 19(12), 2057-64.
Aitken CJ, et al. Regulation of Human Osteoclast Differentiation By Thioredoxin Binding Protein-2 and Redox-sensitive Signaling. J Bone Miner Res. 2004;19(12):2057-64. PubMed PMID: 15537450.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of human osteoclast differentiation by thioredoxin binding protein-2 and redox-sensitive signaling. AU - Aitken,Cathy J, AU - Hodge,Jason M, AU - Nishinaka,Yumiko, AU - Vaughan,Tanya, AU - Yodoi,Junji, AU - Day,Christopher J, AU - Morrison,Nigel A, AU - Nicholson,Geoffrey C, Y1 - 2004/09/20/ PY - 2004/04/05/received PY - 2004/06/21/revised PY - 2004/07/23/accepted PY - 2004/11/13/pubmed PY - 2005/5/6/medline PY - 2004/11/13/entrez SP - 2057 EP - 64 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 19 IS - 12 N2 - UNLABELLED: Differential expression of TBP-2 and Trx-1 occurs during osteoclastogenesis. Adenoviral overexpression of TBP-2 in osteoclast precursors inhibits Trx-1 expression, osteoclast formation, and AP-1 binding activity. TBP-2 and Trx-1 are key regulators of osteoclastogenesis. INTRODUCTION: Thioredoxin binding protein-2 (TBP-2) negatively regulates thioredoxin-1 (Trx-1), a key endogenous modulator of cellular redox and signaling. In gene array analysis, we found that TBP-2 expression was reduced during human osteoclast differentiation compared with macrophage differentiation. Our aim was to determine the roles of TBP-2 and Trx-1 in human osteoclastogenesis and RANKL signaling. MATERIALS AND METHODS: Osteoclasts or macrophages were generated from colony-forming unit-granulocyte macrophage (CFU-GM) precursors treated with sRANKL and macrophage-colony-stimulating factor (M-CSF), or M-CSF alone, respectively. Expression of TBP-2 and Trx-1 was quantified by real-time PCR and Western analysis. Adenoviral gene transfer was used to overexpress TBP-2 in precursors. NF-kappaB and activator protein 1 (AP-1) signaling was assessed with EMSA. RESULTS: In the presence of sRANKL, expression of TBP-2 was decreased, whereas Trx-1 expression was increased. The antioxidant N-acetylcysteine reversed this pattern and markedly inhibited osteoclastogenesis. Adenoviral overexpression of human TBP-2 in precursors inhibited osteoclastogenesis and Trx-1 expression, inhibited sRANKL-induced DNA binding of AP-1, but enhanced sRANKL-induced DNA binding of NF-kappaB. CONCLUSIONS: These data support significant roles for TBP-2 and the Trx system in osteoclast differentiation that are mediated by redox regulation of AP-1 transcription. A likely mechanism of stress signal induction of bone resorption is provided. Modulators of the Trx system such as antioxidants have potential as antiresorptive therapies. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/15537450/Regulation_of_human_osteoclast_differentiation_by_thioredoxin_binding_protein_2_and_redox_sensitive_signaling_ L2 - https://doi.org/10.1359/JBMR.040913 DB - PRIME DP - Unbound Medicine ER -