Selective Androgen Receptor Modulator, YK11, Up-Regulates Osteoblastic Proliferation and Differentiation in MC3T3-E1 Cells

• Published in: Biological & pharmaceutical bulletin Vol. 41; no. 3; pp. 394 - 398
• Main Authors: Yatsu, Tomofumi, Kusakabe, Taichi, Kato, Keisuke, Inouye, Yoshio, Nemoto, Kiyomitsu, Kanno, Yuichiro
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 2018; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: 3T3 Cells; AKT protein; androgen receptor; Androgen receptors; Androgens; Androgens - pharmacology; Animals; Bone mass; Bone mineral density; Calcification, Physiologic - drug effects; Cell Differentiation - drug effects; Cell proliferation; Cell Proliferation - drug effects; Dihydrotestosterone; Gene regulation; MC3T3-E1 cell; Mice; Mineralization; Muscles; Norpregnadienes - pharmacology; Oncogene Protein v-akt - biosynthesis; Oncogene Protein v-akt - genetics; osteoblastic differentiation; Osteoblastogenesis; Osteoblasts; Osteoblasts - drug effects; Osteocalcin; Osteogenesis - drug effects; Osteoprotegerin; Reproductive system; selective androgen receptor modulator; Skeletal muscle; Up-Regulation - drug effects; androgen receptor; osteoblastic differentiation; MC3T3-E1 cell; selective androgen receptor modulator
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b17-00748

Androgens are key regulators that play a critical role in the male reproductive system and have anabolic effects on bone mineral density and skeletal muscle mass. We have previously reported that YK11 is a novel selective androgen receptor modulator (SARM) and induces myogenic differentiation and selective gene regulation. In this study, we show that treatment of YK11 and dihydrotestosterone (DHT) accelerated cell proliferation and mineralization in MC3T3-E1 mouse osteoblast cells. Further, YK11-treated cells increased osteoblast specific differentiation markers, such as osteoprotegerin and osteocalcin, compared to untreated cells. These observations were attenuated by androgen receptor (AR) antagonist treatment. To clarify the effect of YK11, we investigated rapid non-genomic signaling by AR. The phosphorylated Akt protein level was increased by YK11 and DHT treatment, suggesting that YK11 activates Akt-signaling via non-genomic signaling of AR. Because it is known Akt-signaling is a key regulator of androgen-mediated osteoblast differentiation, YK11 has osteogenic activity as well as androgen.