Page 26 - G. Cell differentiation. division. and death

[G. Cell differentiation, division, and death-18]

Blockage of ovariectomy-induced bone loss via suppressing

Ca2+/calmodulin-mediated osteoclast differentiation by a

sphingolipid

Ha Young Lee¹, Kwang Min Cho¹, Min Kyung Kim², Mingyu Lee³, Cheol Yong Choi¹, Kyeong Kyu Kim⁴,

Joon Seong Park⁵, Hong-Hee Kim³, Yoe-Sik Bae¹˙³˙*

¹Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea, ²Cell and Developmental Biology,

BK21 Program and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea, ³Health
Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea, ⁴Precision Medicine,
Institute for Antimicrobial Resistance Research and Therapeutics, Sungkyunkwan University School of , Suwon

16419, Republic of Korea, ⁵Hematology-Oncology, Ajou University School of Medicine, Suwon 16419, Republic of
Korea

Osteoporosis is a disease in which bone mineral density decreases due to excessive activity of osteoclasts. It is
commonly found in postmenopausal women who reduced estrogen levels due to loss of ovarian function due to

aging. Sphingolipids are important biological lipids that can regulate diverse biological responses. However, bone
regulation by sphingolipids is not well discovered. In this study, we found that a sphingolipid strongly inhibits

RANKL-induced osteoclast differentiation. The sphingolipid-induced inhibitory effects on osteoclast differentiation
were not affected by several S1P receptors antagonists or pertussis toxin. However, the sphingolipid inhibited

RANKL-induced calcineurin activation and NFATc1 translocation, leading to decrease of osteoclast related gene
expression. Moreover, we found that bone mineral density was increased by the sphingolipid injection in
ovariectomized (OVX) mouse model, showing increase of BV/TV and Tb.N. The sphingolipid also blocked

ovariectomy-induced body weight increase and Nfatc1 gene expression in mice. Collectively, we suggest that the

sphingolpid has potential as therapeutic agents for osteoporosis treatment.