Effect of pinocembrin isolated from Alpinia zerumbet on osteoblast differentiation
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ORIGINAL ARTICLE
Effect of pinocembrin isolated from Alpinia zerumbet on osteoblast differentiation Noriyuki Natsume . Takayuki Yonezawa
. Je-Tae Woo . Toshiaki Teruya
Received: 30 June 2020 / Accepted: 30 September 2020 Ó Springer Nature B.V. 2020
Abstract Bone mass is regulated by osteoblastmediated bone formation and osteoclast-mediated bone resorption. Osteoporosis is a bone metabolism disorder in which bone mass decreases due to increased bone resorption rather than bone formation. We focused on the traditional plant Alpinia zerumbet in Okinawa, Japan, and searched for promising compounds for the prevention and treatment of osteoporosis. Pinocembrin isolated from the leaves of A. zerumbet showed enhanced alkaline phosphatase (ALP) activity and mineralization and increased mRNA expression of osteoblast-related genes Alp
Takayuki Yonezawa and Toshiaki Teruya contributed equally to this work. N. Natsume T. Teruya (&) Graduate School of Engineering and Science, University of the Ryukyus, 1 Senbaru, Nishihara, Okinawa 903-0213, Japan T. Yonezawa (&) Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan e-mail: [email protected]
and Osteocalcin (Ocn) in MC3T3-E1 cells. Pinocembrin increased the mRNA expression of Runx2 and Osterix, which are important transcription factors in osteoblast differentiation, and the mRNA expression of Dlx5 and Msx2, which are enhancers of these transcription factors. The bone morphogenetic protein (BMP) antagonist noggin, its receptor kinase inhibitor LDN-193189 and p38 MAPK inhibitor SB203580 attenuated pinocembrin-promoted ALP activity. Pinocembrin increased the mRNA of Bmp-2 and its target gene Id1. In addition, the estrogen receptor (ER) inhibitor ICI182780 suppressed pinocembrin-stimulated ALP activity. Pinocembrin may increase BMP-2 expression via ER. Then, the BMP-2 promotes osteoblast specific genes expression and mineralization through both Smad-dependent and independent pathway following Runx2 and Osterix induction. Our findings suggest that pinocembrin has bone anabolic effects and may be useful for the prevention and treatment of bone metabolic diseases such as osteoporosis. Keywords Alpinia zerumbet Pinocembrin Osteoblast differentiation BMP pathway Estrogen receptor
J.-T. Woo Department of Biological Chemistry, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan T. Teruya Faculty of Education, University of the Ryukyus, 1 Senbaru, Nishihara, Okinawa 903-0213, Japan
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Cytotechnology
Introduction Bone mass is maintained by a balance between bone resorption by osteoclasts and bone formation by osteoblasts (Phan et al. 2004; Crockett et al. 2011). This biological mechanism is called ‘‘bone remodeling which is influenced by a number of factors, such as aging, hormonal conditions and lifestyle. Osteoporosis is a metabolic bone disease that has a higher risk of developing in women than in men (Tobias and Compston 1999). Postmenopausal wo
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