Abstract
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.
Highlights
Bone tissue in the skeleton is continuously renewed through bone formation by osteoblasts and bone resorption by osteoclasts [1]
Osteoblasts and osteoclasts play a key role in the formation of the skeleton and regulation of bone mass
Bone loss occurs due to imbalance of osteoblast and osteoclast activity, which causes osteoporosis and increases the risk of fracture [30,31]
Summary
Bone tissue in the skeleton is continuously renewed through bone formation by osteoblasts and bone resorption by osteoclasts [1]. Osteoblasts and osteoclasts play crucial roles in the formation of the skeleton and regulation of bone mass. An imbalance between the formation and function of osteoblasts and osteoclasts can cause diseases, including osteoporosis [2,3]. Subsequent activity depends on the enlargement of osteoclasts and is a major factor controlling bone resorption. Inhibition of osteoclastogenesis does not reverse osteoporosis in elderly people who may have a reduced osteoblast-driven bone formation activity [4], osteoclast activity affects osteogenesis possibly by stimulating osteoblasts either through combined therapy with other drugs or cross-talk between osteoclasts and osteoblasts via the RANKL/RANK/osteoprogeterin triad [5]
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