ECTS Abstracts (2015) 1 P207

Inhibition of osteoclast differentiation by 1,25-dihydroxyvitamin D3 through mTOR signalling pathway

Eunji Kwon1, Bitnara Lee1, Tae-Hwan Kim1 & Jong Dae Ji2

1The Hanyang University Hospital for Rheumatic Diseases, Hanyang University College of Medicine, Seoul, Republic of Korea; 2Rheumatology, College of Medicine, Korea University, Seoul, Republic of Korea.

1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a key molecule to maintain calcium homeostasis and bone metabolism. In addition to the role in calcium homeostasis and bone metabolism, 1,25(OH)2D3 directly inhibits osteoclast differentiation in human and mouse osteoclast precursors. However, the exact mechanism of 1,25(OH)2D3-induced inhibition on osteoclast differentiation remains largely unknown. Recently, mTOR signalling was reported to be involved in osteoclast differentiation. In this study, we showed the role of mTOR signalling pathway in 1,25(OH)2D3-induced inhibition on osteoclast differentiation. 1,25(OH)2D3 strongly inhibited osteoclast differentiation in mouse bone marrow cells and 1,25(OH)2D3-induced inhibition of osteoclast differentiation was significantly reversed by specific inhibitors of mammalian target of rapamycin (mTOR) signalling pathway, including rapamycin and torin 1. 1,25(OH)2D3 induced phosphorylation of p70S6 kinase and Akt, two targets of mTOR complex 1 (mTORC1) and mTORC2, respectively. In addition, 1,25(OH)2D3-induced inhibition of osteoclast differentiation was significantly reversed by Raptor small interfering RNA (siRNA), suggesting that mTORC1 is involved in 1,25(OH)2D3-induced inhibition of osteoclast differentiation. Our results indicate that 1,25(OH)2D3 inhibits osteoclast differentiation through mTOR signalling pathway.

Disclosure: The authors declared no competing interests. Ministry of Education, Science and Technology, Republic of Korea (2012R1A1A2001950, 2014).

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