Page 18 - F. Cell biology

[F. Cell biology-12]

CM inhibits osteoclastogenesis by regulating NF-κB and

attenuates osteoclast maturation via modulating integrin

signaling

Nam Young Kim¹, Hye In Lee¹, Narae Kim¹, Jiae Lee¹, Gong-Rak Lee¹, Minjeong Kwon¹, Hyun Jin Kim¹,

Jin Ha Park¹, Ye Hee Kang¹, Woojin Jeong¹

¹Life Science , Ewha Womans University, Seoul 03760, South KOREA

Excessive osteoclasts cause various bone diseases such as osteoporosis and rheumatoid arthritis. Thus, the regulation

of osteoclast differentiation has clinical implications. CM was identified as an inhibitor of osteoclastogenesis through
drug repositioning approach. Here, we investigated the role of CM in regulating osteoclast differentiation and

elucidated the underlying mechanism. CM inhibited osteoclast formation from bone-marrow derived macrophages,
and it decreased NFATc1 expression along with attenuating NF-κB and activator protein-1 activation, and c-Fos

expression. Immunostaining analysis showed that CM inhibits nuclear translocation of NF-κB. Addition of CM to
differentiated osteoclasts also inhibited osteoclast formation and bone resorption, and reduced integrin β3 and

p130cas expression as well as Rac1 activity. Collectively, these data suggest that CM inhibits osteoclast differentiation
by regulating NF-κB and attenuates osteoclast maturation via modulating integrin signaling. Furthermore, CM

protected bone destruction in lipopolysaccharide- and ovariectomy-induced osteolytic mouse models, which
strongly supports its usefulness as a potential drug to treat inflammation-induced bone diseases and

postmenopausal osteoporosis.