Cyperus Rotundus L. extract suppresses RANKL-induced osteoclastogenesis through NFATc1/c-fos downregulation and prevent bone loss in OVX-induced osteoporosis rat.
BACKGROUND
Cyperus Rotundus L. (CyR) has been widely used for the treatment of gynecologic disorder. Recent studies have reported that CyR can prevent the formation of cystic follicles and ovarian malfunction. However, the effects of CyR on osteoclastogenesis and postmenopausal osteoporosis remain unknown.


OBJECTIVE
This study was aimed to investigate the preventive effects of CyR on RANKL-induced osteoclast formation and ovariectomy (OVX)-induced bone loss.


METHODS
In this in vitro study, we investigate the anti-osteoporotic effect of CyR on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis, the formation of tartrate-resistant acid phosphatase (TRAP) multinucleated cells, pit formation, transcription factors such as NFATc1 and c-Fos, and mRNA expression of osteoclast-associated genes were investigated. Forty 12-weeks female Sprague-Dawley rats for in vivo effect of CyR were used and OVX rat model was determined. The rats were randomly assigned into sham group and four OVX groups, i.e. OVX with D.W; OVX with estradiol (E2, 100μg/kg/day), OVX with CyR-L (16mg/kg/day), OVX with CyR-H (160mg/kg/day). The treatment lasted for 8weeks.


RESULTS
CyR inhibited osteoclast differentiation and pit formation in the RANKL-induced osteoclastogenesis of RAW 264.7 cells. Reverse transcription polymerase chain reaction analysis also showed that CyR reduced the mRNA expression of osteoclast-associated genes such as carbonic anhydrase II, TRAP, RANK, cathepsin K, matrix metalloproteinase 9, nuclear factor of activated T cells cytoplasmic 1 (NFATc1), and c-Fos. In addition, CyR decreased protein levels of NFATc1 and c-Fos. CyR inhibited trabecular bone loss in the femur caused by OVX.


CONCLUSIONS
The results of this study indicate that CyR inhibits the RANKL-induced osteoclast differentiation in RAW 264.7 cells and trabecular bone loss in OVX rats.
Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 02447, South Korea.
Chang-Jun
CJ
Kum
Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 02447, South Korea.
Eun-Young
EY
Kim
Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 02447, South Korea.
Jae-Hyun
JH
Kim
Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 02447, South Korea.
Bina
B
Lee
Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 02447, South Korea.
Ju-Hee
JH
Min
Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 02447, South Korea.
Jun
J
Heo
Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 02447, South Korea.
Jong-Hyun
JH
Kim
Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, South Korea.
Mijung
M
Yeom
Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 02447, South Korea.
Youngjoo
Y
Sohn
Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 02447, South Korea. Electronic address: jhs@khu.ac.kr.
Hyuk-Sang
HS
Jung
D000818:Animals; D050071:Bone Density Conservation Agents / Q000737:chemistry / Q000494:pharmacology; D029786:Cyperus / Q000737:chemistry*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000235:genetics / Q000502:physiology*; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D010024:Osteoporosis / Q000517:prevention & control; D010052:Ovariectomy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D050071:Bone Density Conservation Agents; C584440:NFATC1 protein, rat; D010936:Plant Extracts; D053245:RANK Ligand; D014157:Transcription Factors
C-Fos; Cyperus Rotundus L.; Nuclear factor of activated T-cells cytoplasmic 1; Osteoclastogenesis; Ovariectomy; Receptor activator of the nuclear factor kappa B ligand