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

• Published in: International journal of molecular sciences 2018-11, Vol.19 (11), p.3436
• Main Authors: Cho, Eugene, Lee, Jin-Kyung, Lee, Jee-Young, Chen, Zhihao, Ahn, Sun-Hee, Kim, Nam Doo, Kook, Min-Suk, Min, Sang Hyun, Park, Byung-Ju, Lee, Tae-Hoon
• Format: Article
• Language: English
• Subjects: Acid phosphatase; Acid phosphatase (tartrate-resistant); Acid resistance; Acrylamide; Acrylamides - chemistry; Acrylamides - toxicity; Animals; BCPA; Binding sites; Biomedical materials; Bone diseases; Butanes - chemistry; Butanes - toxicity; c-Fos protein; Cell cycle; Cell Death - drug effects; Cell Differentiation - drug effects; Cell fusion; Cell Line; Computer Simulation; Cytotoxicity; DC-STAMP; DC-STAMP protein; Dendritic cells; Differentiation; Fractures; Fusion protein; Gene expression; Juglone; Leukocytes (mononuclear); Lymphocytes; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice, Inbred C57BL; Mitosis; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; NF-AT protein; NIMA-Interacting Peptidylprolyl Isomerase - chemistry; NIMA-Interacting Peptidylprolyl Isomerase - metabolism; Older people; osteoclast; Osteoclastogenesis; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - enzymology; Osteogenesis - drug effects; Osteoporosis; Peptidylprolyl isomerase; Phosphorylation; Pin1; Pin1 protein; Polyethylene glycol; Proteins; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; TRANCE protein; Transcription factors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19113436

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 , '-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 mRNA levels. BCPA repressed the expression of osteoclast-related genes, such as and osteoclast-associated receptor ( ), without altering the mRNA expression of nuclear factor of activated T cells ( ) and cellular oncogene 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.