Regulation of osteoclastogenesis by Simon extracts composed of caffeic acid and related compounds: successful suppression of bone destruction accompanied with adjuvant-induced arthritis in rats.
Simon extracts are vitamin K(1)-rich food materials extracted from the leaves of the Simon sweet potato. Although vitamin K is known to stimulate bone formation, we postulated that Simon extracts also contain unknown biological compounds having the ability to regulate bone resorption. Here we prepared the vitamin K-free fraction from the Simon extracts and investigated the ability of this fraction on the differentiation of osteoclasts. A remarkable inhibitory effect of osteoclastogenesis was observed when osteoclast precursors were treated with this fraction in rat bone marrow culture systems as well as in a pure differentiation system using murine osteoclast precursor cell line. The vitamin K-free Simon extracts markedly suppressed severe bone destruction mediated by abundant osteoclasts associated with adjuvant-induced arthritis in rats. High performance liquid chromatography (HPLC) analysis revealed that the vitamin K-free Simon extracts contained three types of low molecular weight inhibitors for osteoclastogenesis; caffeic acid, chlorogenic acids and isochlorogenic acids. Among these substances, caffeic acid showed the most powerful inhibitory effects on osteoclastogenesis. Caffeic acid significantly suppressed expression of NFATc1, a key transcription factor for the induction of osteoclastogenesis. Our current study enlightened a high utility of the Simon extracts and their chemical components as effective regulators for bone resorption accompanied with inflammation and metabolic bone diseases.
Tang
Quan Yong
QY
Oral Cellular and Molecular Biology, Kyushu University, Maidashi 3-1-1, Fukuoka, 812-8582, Japan.
Kukita
Toshio
T
Ushijima
Yuki
Y
Kukita
Akiko
A
Nagata
Kengo
K
Sandra
Ferry
F
Watanabe
Toshiyuki
T
Toh
Kazuko
K
Okuma
Yutaka
Y
Kawasaki
Sadamichi
S
Rasubala
Linda
L
Teramachi
Junpei
J
Miyamoto
Ichiko
I
Wu
Zhou
Z
Iijima
Tadahiko
T
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D001483:Base Sequence; D001862:Bone Resorption / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002109:Caffeic Acids / Q000494:pharmacology*; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D066298:In Vitro Techniques; D027723:Ipomoea batatas / Q000737:chemistry; D008297:Male; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014812:Vitamin K / Q000302:isolation & purification
D002109:Caffeic Acids; D017931:DNA Primers; D010936:Plant Extracts; D053246:Receptor Activator of Nuclear Factor-kappa B; D014812:Vitamin K; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D002403:Cathepsins; D056657:Cathepsin K; C534133:Ctsk protein, rat; C040048:caffeic acid