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BCPA {N,N′-1,4-Butanediylbis[3-(2-chlorophenyl)acrylamide]} Inhibits Osteoclast Differentiation through Increased Retention of Peptidyl-Prolyl cis-trans Isomerase Never in Mitosis A-Interacting 1

1
Department of Oral Biochemistry, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 61186, Korea
2
Department of Molecular Medicine (BK21plus), Chonnam National University Graduate School, Gwangju 61186, Korea
3
New Drug Development Center, DGMIF, 80 Chumbok-ro, Dong-gu, Daegu 41061, Korea
4
NDBio Therapeutics Inc., S24 Floor, Songdogwahak-ro 32, Yeonsu-gu, Incheon 21984, Korea
5
Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University, Gwangju 61186, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(11), 3436; https://doi.org/10.3390/ijms19113436
Received: 12 September 2018 / Revised: 29 October 2018 / Accepted: 30 October 2018 / Published: 1 November 2018
(This article belongs to the Section Biochemistry)
Osteoporosis is caused by an imbalance of osteoclast and osteoblast activities and it is characterized by enhanced osteoclast formation and function. Peptidyl-prolyl cis-trans isomerase never in mitosis A (NIMA)-interacting 1 (Pin1) is a key mediator of osteoclast cell-cell fusion via suppression of the dendritic cell-specific transmembrane protein (DC-STAMP). We found that N,N′-1,4-butanediylbis[3-(2-chlorophenyl)acrylamide] (BCPA) inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in a dose-dependent manner without cytotoxicity. In addition, BCPA attenuated the reduction of Pin1 protein during osteoclast differentiation without changing Pin1 mRNA levels. BCPA repressed the expression of osteoclast-related genes, such as DC-STAMP and osteoclast-associated receptor (OSCAR), without altering the mRNA expression of nuclear factor of activated T cells (NFATc1) and cellular oncogene fos (c-Fos). Furthermore, Tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells were significantly decreased by BCPA treatment compared to treatment with the Pin1 inhibitor juglone. These data suggest that BCPA can inhibit osteoclastogenesis by regulating the expression of the DC-STAMP osteoclast fusion protein by attenuating Pin1 reduction. Therefore, BCPA may be used to treat osteoporosis. View Full-Text
Keywords: Pin1; DC-STAMP; BCPA; osteoclast; osteoporosis Pin1; DC-STAMP; BCPA; osteoclast; osteoporosis
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Cho, E.; Lee, J.-K.; Lee, J.-Y.; Chen, Z.; Ahn, S.-H.; Kim, N.D.; Kook, M.-S.; Min, S.H.; Park, B.-J.; Lee, T.-H. BCPA {N,N′-1,4-Butanediylbis[3-(2-chlorophenyl)acrylamide]} Inhibits Osteoclast Differentiation through Increased Retention of Peptidyl-Prolyl cis-trans Isomerase Never in Mitosis A-Interacting 1. Int. J. Mol. Sci. 2018, 19, 3436.

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