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

• Main Authors: Eugene Cho, Jin-Kyung Lee, Jee-Young Lee, Zhihao Chen, Sun-Hee Ahn, Nam Doo Kim, Min-Suk Kook, Sang Hyun Min, Byung-Ju Park, Tae-Hoon Lee
• Format: Article
• Language: English
• Published: MDPI AG 2018-11-01
• Series: International Journal of Molecular Sciences
• Subjects: Pin1; DC-STAMP; BCPA; osteoclast; osteoporosis
• Online Access: https://www.mdpi.com/1422-0067/19/11/3436

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 <i>N</i>,<i>N</i>&#8242;-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 <i>Pin1</i> mRNA levels. BCPA repressed the expression of osteoclast-related genes, such as <i>DC-STAMP</i> and osteoclast-associated receptor (<i>OSCAR</i>), without altering the mRNA expression of nuclear factor of activated T cells (<i>NFATc1</i>) and cellular oncogene fos (<i>c-Fos</i>). 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.