Chung Hwa-Jin, Cho Lan, Shin Joon-Shik, Lee Jinho, Ha In-Hyuk, Park Hyen Joo, Lee Sang Kook
College of Pharmacy, Natural Products Research Institute, Seoul National University, San 56-1 Sillim-dong, Gwanak-gu, Seoul 151-742, Korea.
BMC Complement Altern Med. 2014 Jun 6;14:184. doi: 10.1186/1472-6882-14-184.
JSOG-6 is used as a traditional medicine to relieve the symptoms associated with inflammation, rheumatism, and osteoporosis in Korea. In the present study, we investigated the effects of JSOG-6 on bone loss prevention both in in vitro and in vivo as well as its underlying mechanism of action.
Protection against bone loss was assessed in an ovariectomized (OVX) mouse model. Bone microarchitecture was measured using a micro-computed tomography to detect the parameters of three-dimensional structure of a trabecular bone. Serum biomarkers were also evaluated in an OVX-induced model. Osteoclasts derived from mouse bone marrow cells (BMCs) and osteoblastic MC3T3-E1 cells were also employed to investigate the mechanism of action.
Oral administration of JSOG-6 significantly increased the bone mineral density (BMD) of the femur in OVX mice in vivo. Especially, the reduced Tb.No (trabecular bone number) in the OVX group was significantly recovered by JSOG-6 treatment. The serum levels of alkaline phosphatase (ALP), osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase, biomarkers of bone resorption, were significantly elevated in OVX mice, but JSOG-6 effectively inhibited the increase in OVX mice. JSOG-6 was also found to enhance the osteoblastic differentiation and maturation with the increase of the density and ALP activity, a marker of osteoblastic differentiation, as well as calcium deposition, a marker of osteoblastic maturation in MC3T3-E1 cells. The effects of JSOG-6 on osteoblastic differentiation were also associated in part with the increase of ALP and OPN mRNA expressions and the decrease of RANKL mRNA expression in MC3T3-E1 cells.
The findings demonstrate that JSOG-6 induced protection against bone loss in OVX mice, and its anti-osteoporotic property might be, in part, a function of the stimulation of osteoblast differentiation and the inhibition of osteoclast formation. These findings suggest that JSOG-6 might be an applicable therapeutic traditional medicine for the regulation of the osteoporotic response.
在韩国，JSOG - 6作为一种传统药物用于缓解与炎症、风湿和骨质疏松相关的症状。在本研究中，我们研究了JSOG - 6在体外和体内预防骨质流失的作用及其潜在作用机制。
在去卵巢（OVX）小鼠模型中评估对骨质流失的保护作用。使用微型计算机断层扫描测量骨微结构，以检测小梁骨三维结构的参数。还在OVX诱导的模型中评估血清生物标志物。源自小鼠骨髓细胞（BMC）的破骨细胞和成骨MC3T3 - E1细胞也用于研究作用机制。
在体内，口服JSOG - 6显著增加了OVX小鼠股骨的骨矿物质密度（BMD）。特别是，JSOG - 6治疗显著恢复了OVX组中降低的骨小梁数量（Tb.No）。OVX小鼠中骨吸收的生物标志物碱性磷酸酶（ALP）、骨钙素、C末端肽和抗酒石酸酸性磷酸酶的血清水平显著升高，但JSOG - 6有效抑制了OVX小鼠中的升高。还发现JSOG - 6随着成骨细胞分化标志物密度和ALP活性以及成骨细胞成熟标志物钙沉积的增加，增强了成骨细胞的分化和成熟，在MC3T3 - E1细胞中。JSOG - 6对成骨细胞分化的影响也部分与MC3T3 - E1细胞中ALP和OPN mRNA表达的增加以及RANKL mRNA表达的降低有关。
研究结果表明，JSOG - 6可诱导对OVX小鼠骨质流失的保护作用，其抗骨质疏松特性可能部分是刺激成骨细胞分化和抑制破骨细胞形成的作用。这些发现表明，JSOG - 6可能是一种适用于调节骨质疏松反应的治疗性传统药物。
