Oleanolic acid exerts an osteoprotective effect in ovariectomy-induced osteoporotic rats and stimulates the osteoblastic differentiation of bone mesenchymal stem cells in vitro

Bian, Qin; Liu, Shu Fen; Huang, Jian; Yang, Zhu; Tang, De Zhi; Zhou, Quan; Ning, You; Zhao, Yuechao; Lü, Sheng; Shen, Zi Yin; Wang, Yong Jun

doi:10.1097/gme.0b013e3182272ef1

Cited by 47 publications

(33 citation statements)

References 27 publications

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“…Previous studies conducted by our laboratory demonstrated that an ethanol extract of FLL may increase bone mineral density and improve bone mechanical properties in growing female rats (22), and upregulate calcium absorption-associated gene expression in the kidney and duodenum (23). In additfion, it has been revealed to downregulate the gene expression ratio of RANKL/osteoprotegerin in MC3T3-E1 cells (an osteoblast-like cell line) (24). However, the effect of FLL on osteoclast differentiation and bone resorption, and its underlying mechanism, remain to be elucidated, and the active compounds present in FLL have not yet been identified.…”

Section: Fructus Ligustri Lucidi Ethanol Extract Inhibits Osteoclastomentioning

confidence: 89%

“…Oleanolic acid (OA) and ursolic acid (UA) are two primary active components in FLL extract. Certain studies have indicated that OA (or its derivative) may inhibit osteoclastogenesis and mRNA expression levels of bone-associated genes in vitro (24,25); however, the effect of UA on osteoclast differentiation and bone resorption, to the best of our knowledge, remains to be elucidated. The present study aims to elucidate the effect of FLL on osteoclasts, and its underlying mechanism, and to identify the active ingredients.…”

Section: Fructus Ligustri Lucidi Ethanol Extract Inhibits Osteoclastomentioning

confidence: 98%

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Fructus Ligustri Lucidi ethanol extract inhibits osteoclastogenesis in RAW264.7 cells via the RANKL signaling pathway

Lyu

Chen

et al. 2016

Molecular Medicine Reports

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Fructus ligustri Lucidi (FLL) is the fruit of Ligustrum lucidum Ait and a traditional Chinese medicine, primarily known for its role in osteoporosis prevention and treatment. The present study aimed to elucidate the effect and underlying mechanism of action of ethanol extract of FLL on osteoclast differentiation and bone resorption, and to identify the active compounds within it. RAW264.7 murine monocyte/macrophage cells were stimulated with the receptor activator of nuclear factor κB ligand (RANKL) to induce osteoclast differentiation in vitro. The present study demosntrated that FLL extract and its two primary components, oleanolic acid (OA) and ursolic acid (UA), significantly suppressed RANKL‑induced tartrate resistant acid phosphatase (TRAP) activity and multinucleate osteoclast formation without inducing cytotoxicity; however, no effect was observed on the apoptosis of mature osteoclasts. Additionally, RANKL‑induced mRNA expression levels of the key transcription factors, tumor necrosis factor receptor associated factor‑6, nuclear factor of activated T cell‑c1 and c‑Fos, and the osteoclast markers, TRAP, cathepsin K and matrix metalloproteinase‑9 were suppressed by FLL, OA and UA. However, no effect was observed on RANKL‑induced mRNA expression levels of Src. These results demonstrated that FLL may inhibit osteoclastogenesis in RAW264.7 cells via RANKL signaling pathways. OA and UA are active compounds in inducing this effect; however, their specific roles remain to be elucidated.

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Section: Fructus Ligustri Lucidi Ethanol Extract Inhibits Osteoclastomentioning

confidence: 89%

Section: Fructus Ligustri Lucidi Ethanol Extract Inhibits Osteoclastomentioning

confidence: 98%

Fructus Ligustri Lucidi ethanol extract inhibits osteoclastogenesis in RAW264.7 cells via the RANKL signaling pathway

Lyu

Chen

et al. 2016

Molecular Medicine Reports

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“…Oleanolic acid was reported to have an osteoprotective effect in rats with ovariectomy-induced osteoporosis; its ability to stimulate osteoblastic differentiation might be related to the Notch signaling pathway [69]. Li et al .…”

Section: Gene Expression Studiesmentioning

confidence: 99%

Genome-wide approaches for identifying genetic risk factors for osteoporosis

Liu

Zhang

et al. 2013

Genome Medicine

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Osteoporosis, the most common type of bone disease worldwide, is clinically characterized by low bone mineral density (BMD) and increased susceptibility to fracture. Multiple genetic and environmental factors and gene-environment interactions have been implicated in its pathogenesis. Osteoporosis has strong genetic determination, with the heritability of BMD estimated to be as high as 60%. More than 80 genes or genetic variants have been implicated in risk of osteoporosis by hypothesis-free genome-wide studies. However, these genes or genetic variants can only explain a small portion of BMD variation, suggesting that many other genes or genetic variants underlying osteoporosis risk await discovery. Here, we review recent progress in genome-wide studies of osteoporosis and discuss their implications for medicine and the major challenges in the field.

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“…27 Small molecule compounds from herbal medicine can also exert bone protective effects by suppressing osteoclast-activated bone resorption function. 30,31 Our recently investigation has fully identified that OA also strongly inhibits the early stage of osteoclastogenesis thus attenuates osteoporotic phenotypes in OVX mice. 30,31 Our recently investigation has fully identified that OA also strongly inhibits the early stage of osteoclastogenesis thus attenuates osteoporotic phenotypes in OVX mice.…”

Section: Introductionmentioning

confidence: 99%

Oleanolic acid exerts inhibitory effects on the late stage of osteoclastogenesis and prevents bone loss in osteoprotegerin knockout mice

Zhao

Shu

Wang

et al. 2019

J of Cellular Biochemistry

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Postmenopausal women undergo rapid bone loss, which caused by the accelerated osteoclastic bone resorption. Receptor activator of nuclear factor kappa‐B ligand (RANKL) plays critical and essential roles on varied stages of osteoclastogenesis. Oleanolic acid (OA), a naturally derived small compound, has been found suppress osteoclastogenesis in early stage of bone marrow macrophages (BMMs). However, whether OA also regulates the late stage of osteoclastogenesis remains unclear. Here, the regulatory effect of OA on the late stage of osteoclastogenesis was investigated in vitro using RANKL‐pretreated BMMs and in vivo using osteoprotegerin (OPG) knockout mice. Our in vitro studies demonstrate that OA inhibits the late stage of osteoclastogenesis from RANKL‐pretreated BMMs. For in vivo animal investigation, OA attenuates the bone loss phenotypes in OPG‐knockout mice by decreasing the densities of osteoclast, which are in consistent with the finding with in vitro osteoclastogenesis. Mechanistic investigations found that OA largely inhibit the activity of c‐Fos and Nuclear factor of activated T‐cells c1 (NFATc1) with RANKL‐pretreated BMMs and OPG‐knockout mice. Furthermore, OA suppresses the activities of osteoclast genes, such as Tartrate resistant acid phosphatase (TRAP), CathepsinK (Ctsk), and Matrix metalloproteinase 9 (MMP9). Taken together these findings, they have not only defined an inhibitory effect of OA in the late stage of osteoclastogenesis but have also gained new molecular mechanisms underlying the process of osteoclast formation.

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Oleanolic acid exerts an osteoprotective effect in ovariectomy-induced osteoporotic rats and stimulates the osteoblastic differentiation of bone mesenchymal stem cells in vitro

Abstract: OA exerts an osteoprotective effect in OVX-induced osteoporotic rats and stimulates the osteoblastic differentiation of bMSCs in vitro. The molecular mechanism of this effect might be related to the Notch signaling pathway and requires further investigation.

Cited by 47 publications

References 27 publications

Fructus Ligustri Lucidi ethanol extract inhibits osteoclastogenesis in RAW264.7 cells via the RANKL signaling pathway

Fructus Ligustri Lucidi ethanol extract inhibits osteoclastogenesis in RAW264.7 cells via the RANKL signaling pathway

Genome-wide approaches for identifying genetic risk factors for osteoporosis

Oleanolic acid exerts inhibitory effects on the late stage of osteoclastogenesis and prevents bone loss in osteoprotegerin knockout mice

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